Luis Hernandez - Academia.edu (original) (raw)
Papers by Luis Hernandez
Psychopharmacology, 1991
Cocaine and two other local anesthetics were applied directly into the nucleus accumbens for 20 m... more Cocaine and two other local anesthetics were applied directly into the nucleus accumbens for 20 min by diffusion from a 4 mm microdialysis probe in freely moving rats. Cocaine (7.3 mM) increased the extracellular concentration of dopamine (DA). Equimolar procaine did also, but was not as potent as cocaine. Equimolar lidocaine had no effect. The concentration of these drugs outside the probe as measured by capillary electrophoresis in vitro was about 28% of that inside the probe, i.e. 72% remained inside. However, an in vivo test showed that about 53% cocaine and procaine, and 37% lidocaine remained in the perfusion fluid after passing through a probe inserted in the brain. This suggests that in vivo about 68 nmol cocaine diffused into the nucleus accumbens (NAC) during the 20 min. Five conclusions are drawn: (1) this confirms our earlier finding that local injection of cocaine increases extracellular DA, but in this case the cocaine was infused via the probe without disturbing the animal; (2) the action of cocaine on dopamine terminals in the accumbens is independent of local anesthesia; (3) procaine may enhance mood by a cocaine-like effect; (4) capillary electrophoresis has potential for measuring cocaine levels in small samples and (5) in vitro calibrations are of limited value to evaluate in vivo performance of microdialysis probes.
Brain Research Bulletin, 1990
Fluctuations of cortical dopamine during feeding were examined by in vivo microdialysis. Dopamine... more Fluctuations of cortical dopamine during feeding were examined by in vivo microdialysis. Dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured by high performance liquid chromatography and electrochemical detection. Food-deprived rats were trained to eat by pressing a bar for food when a light and a feeder were turned on. The day of the experiment a microdialysis probe was inserted in the prefrontal cortex (PFC) of the rats and dialysates were collected every 20 minutes while the light and the feeder were off. When the neurochemical baseline was stable the light and the feeder were turned on for 20 minutes only. During this time the rats ate (mean 204 pellets = 9.2 g) and DA increased about 55%, remained high for another 20 minutes and then gradually returned toward baseline levels. DOPAC increased 30% in the first 20 minutes after the eating bout. HVA increased 40 minutes after the eating bout. Histology showed the probes were located in the anteromedial region of the PFC. We conclude that dopamine turnover in the mesocortical system increases during feeding under the conditions used. The results are discussed in terms of the role of the PFC in food intake modulation.
Brain Research Bulletin, 1994
TUCCI, S., R. FERNANDEZ, T. BAPTISTA, E. MURZI AND L. HERNANDEZ. Dopamine increase in rhe prefron... more TUCCI, S., R. FERNANDEZ, T. BAPTISTA, E. MURZI AND L. HERNANDEZ. Dopamine increase in rhe prefrontal cortex correlates with reversal of haloperidol-induced catalepsy in rats. BRAIN RES BULL 35(2) 125-133, 1994.-The mechanism by which forced swimming reverses haloperidol-induced catalepsy was examined by measuring dopamine (DA) turnover in the nucleus accumbens-ventromedial caudate (NAC-C) and the prefrontal cortex (PFC) in rats. DA and its metabolites 3,4-dihydroxiphenylacetic acid (DOPAC) and homovanillic acid (HVA) were assessed by microdialysis and high pressure liquid chromatography with electrochemical detection (HPLC-ED) after systemic administration of a cataleptic dose of haloperidol (5 mg/kg) or saline. Haloperidol-induced catalepsy was temporarily suppressed by forced swimming. Haloperidol-treated rats showed an increase of DA, DOPAC, and HVA overflow in the PFC and the NAC-C. This increase was greater in the PFC of rats that were forced to swim. Rats that were not treated with haloperidol but were forced to swim (control group) showed an increase of DA, DOPAC, and HVA in the PFC but not in the NAC-C. Zero micrograms, 5 pg, 10 pg. and 20 pg of DA was bilaterally injected in the PFC of cataleptic rats to evaluate the hypothesis that DA in the PFC reverses catalepsy. Haloperidol-induced catalepsy was diminished by bilateral microinjections of IO pg and 20 pg but not by 5 pg of DA in the PFC. The higher the dose of DA, the longer the decrease of catalepsy. These results suggest that an increase of DA turnover in the PFC might mediate temporal suppression of haloperidol-induced catalepsy. The mechanism by which the mesocortical DA system reduces catalepsy is discussed.
Brain Research, 1989
Microdialysis was used to monitor serotonin, 5-hydroxyindoleacetic acid (5-HIAA) and the metaboli... more Microdialysis was used to monitor serotonin, 5-hydroxyindoleacetic acid (5-HIAA) and the metabolites of dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the perifornical lateral hypothalamus (PFH) of freely moving rats. Systemically administered d-fenfluramine (d-FEN) increased extracellular serotonin, DOPAC and HVA, while decreasing serotonin's metabolite 5-HIAA. Local application of d-FEN directly to the hypothalamic terminal region caused large increases in extracellular serotonin and had a tendency to decrease all 3 metabolites. This effect was confirmed when d-FEN was infused locally by reverse dialysis. These results provide direct evidence that the anorectic drug d-FEN can increase extracellular serotonin in the hypothalamus in vivo and suggest a serotonergic action in the perifornical region. This finding is consistent with our report that a meal also increases serotonin in this region.
Brain Research, 1982
Earlier research from this laboratory showed that 6-hydroxydopamine (6-OHDA) injected into the ve... more Earlier research from this laboratory showed that 6-hydroxydopamine (6-OHDA) injected into the ventral midbrain of rats causes overeating and the gradual development of obesity in association with extensive depletion of forebrain norepinephrine. It was proposed that depletion of norepinephrine or epinephrine was the cause of the behavioral abnormality. This was questioned on the basis of experiments showing that 6-OHDA can cause non-selective lesions and also that non-selective neurotoxins can cause hyperphagia. To help resolve this question, the present experiments used 191 rats in 28 groups to test 3 doses of 6-OHDA and 3 different pretreatments with reuptake blockers, amphetamine, desmethylimipramine and benztropine. The result of midbrain 6-OHDA alone was hyperphagia that was highly correlated with the dose. Pretreatment with intraperitoneal desmethylimipramine (DMI) caused gastric distress, and systemic amphetamine caused delayed overeating, but these unwanted side effects were avoided by injecting the drugs directly into the midbrain 15 min before the 6-OHDA. DMI and amphetamine partially prevented catecholamine depletion in the forebrain and totally prevented subsequent hyperphagia and obesity. Benztropine prevented dopamine depletion, but had no effect on hyperphagia. We conclude that some of the neurons protected by local injection of amphetamine and DMI are probably norepinephrine or epinephrine fibers that ascend through the ventral midbrain and have as one of their functions the inhibition of food intake. These neurons could also play a role in the control of body weight.
Pharmacology Biochemistry and Behavior, 1989
Daily rhythms in extracellular levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-... more Daily rhythms in extracellular levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were examined in the region of the paraventricular nucleus (PVN), using intracerebral microdialysis combined with high performance liquid chromatography and electrochemical detection. Samples of PVN dialysate, from 11 rats on a 12/12 hr light/dark cycle, were collected and assayed for 5-HIAA every 2 hr for 3 days. During the first 2 days the rats were given free access to food. During the 3rd day they were deprived of food for a 24-hr period and then given food for 4 hr. The results showed that in freely-feeding rats, there was a 24-hr rhythm in the levels of 5-HIAA, with a marked transient peak just after the beginning of the dark portion of the light/dark cycle and stable levels at all other times. When the animals were food-deprived, PVN levels of this metabolite remained stable, and the early dark peak was abolished, suggesting that it might have been consequent to the eating behavior which normally occurred at this time. In the 4-hr refeeding period, there were no changes in 5-HIAA levels, despite the intense eating behavior which occurred during this time. These patterns of 5-HIAA in the PVN region, taken together with previous evidence, suggest that PVN serotonin metabolism may increase in association with feeding specifically in the early portion of the nocturnal eating period, when it may play a role in controlling food intake and macronutrient selection.
Pharmacology Biochemistry and Behavior, 1987
BAPTISTA, T , M PARADA AND L HERNANDEZ Long term admmtstratton of some anttpsychottc drugs mcreas... more BAPTISTA, T , M PARADA AND L HERNANDEZ Long term admmtstratton of some anttpsychottc drugs mcreases body wetght and feeding in rats Are D2 dopamme receptors tnvolved~ PHARMACOL BIOCHEM BEHAV 27(3) 399-405, 1987 --Long term admlmstratlon of the antlpsychoUc drugs tluondazlne, tnfluoperazme, hatopendol, and sulpmde mcreased body weight m rats Th~s effect was found to be sex dependent, that is, while female rats were prone to gain weight, male rats did not Chlorpromazme and fluphenazme decreased body weight m male rats but did not affect females The mechamsm of body wetght gain was mvesttgated w~th sulpmde A hnear relatmnshlp between dose of sulpmde and body weight gain was found Also, sulpmde increased caloric retake, and both actions were counteracted by bromocnptme, a spectfic D2 receptor agomst These results confirm that antlpsychotlc drugs affect feeding and body weight and suggest that hyperphagla and body weight gain might be medmted by blockade of dopamlne receptors of the D2 type Antlpsychotlc drugs Bromocnptme Body weight Feeding Dopamlne D2 receptors
Pharmacology, 1978
Phenylpropanolamine hydrochloride (PPA) is a widely used decongestant and anorectic drug. The pre... more Phenylpropanolamine hydrochloride (PPA) is a widely used decongestant and anorectic drug. The present study investigated the hypoglycemic effects of intraperitoneal PPA on rats to test the possibility that it might derive some of its anorectic properties through effects on glucostatic mechanisms. PPA tended to lower blood glucose levels in normal rats; the glycemia reducing effect was larger and statistically significant in rats made hyperglycemic by prior treatment with streptozocin to cause diabetes. This is the first evidence that PPA migh possibly reduce feeding by increasing blood sugar utilization.
Brain Research Bulletin, 1990
In the present experiments we extend previous findings that established a relationship between fe... more In the present experiments we extend previous findings that established a relationship between feeding behavior and hypothalamic serotonin as measured by in vivo microdialysis. The new result is hypothalamic release of serotonin in anticipation of eating when the animal sees and smells food. We have now verified brain serotonin peaks in four different ways: 1) a serotonergic reuptake blocker (fluoxetine 1 or 10 μM) in the perfusion medium raised basal levels of serotonin.2) every sample was oxidized at two potentials using a dual potentiostat to confirm the voltage characteristics of each peak.3) serotonin peaks were reduced by the selective serotonin cell body agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), thus helping confirm that most of the serotonin observed in these experiments was neuronal in origin, and 4) lateral and medial hypothalamic microdialysis probes were used simultaneously to monitor the degree of diffusion from one to the other. The results show that extracellular serotonin increases at both sites during preingestive events as well as during eating, but not afterwards.
Annals of The New York Academy of Sciences, 1989
To help understand the neurochemical basis of behavior reinforcement, we have perfected the techn... more To help understand the neurochemical basis of behavior reinforcement, we have perfected the technique of in vivo microdialysis for studying brain functions in behaving animals. Monoamines and their main metabolites were sampled in the extracellular space of the hypothalamus or nucleus accumbens in rats given food, water, salt, anorectic drugs, conditioned taste aversion, or addictive psychomotor stimulants. This has contributed to the view that in the paraventricular nucleus (PVN) norepinephrine facilitates feeding and serotonin inhibits it; in the perifornical lateral hypothalamus (PFH), the monoamines contribute to inhibition of feeding; and in the nucleus accumbens (NAC), dopamine facilitates positive reinforcement. Microdialysis results are summarized in the last paragraph. To put the new results in the context of eating disorders, we begin with a review of earlier monoamine depletion and injection studies.
Psychopharmacology, 1983
Rats learned to self-administer d-amphetamine (10 μg/μl) through a cannula implanted in the nucle... more Rats learned to self-administer d-amphetamine (10 μg/μl) through a cannula implanted in the nucleus accumbens. They responded more frequently for 65±15 nl of amphetamine than for equal amounts of saline. When presented with two levers (one amphetamine, one blank) they responded more on the correct lever for amphetamine. They would also switch levers, when necessary, to maintain access to the drug. When half the usual drug intake was given automatically, animals reduced their response rate by half, thus self-regulating the total amount of amphetamine they received. In tests for leakage into the ventricles, eight rats that self-injected with an accumbens cannula showed response extinction when switched to a ventricular cannula. We conclude that amphetamine self-injected into the accumbens is a positive reinforcer. This localization of ‘amphetamine reward’ suggests that the nucleus accumbens contains a synaptic mechanism underlying amphetamine abuse and, perhaps, also natural reinforcement of behavior.
Brain Research Bulletin, 1987
~rt/rn,7c,r,rr.s tr7ic,rcrclicr/~sis and crmphctcminr, injbsion in the nw/~~~s crc~c~rcmhor.s and... more ~rt/rn,7c,r,rr.s tr7ic,rcrclicr/~sis and crmphctcminr, injbsion in the nw/~~~s crc~c~rcmhor.s and striatrrm c!ffrz~!\: mo~+ng rats: Inc~rcwsc~ i/l r.utrrrc~c~//rt/nr doprrrxitle rrnd serofotzin. BRAIN RES BULL 19(6f 623-628, 1987.-To test the effects of systemic and local amphetamine on dopamine and serotonin release in freely moving rats, guide cannulas were implanted in the nucleus accumbens and ventral striatum for removable 200 i* microdialysis probes. Comparing 4.5 min samples before and after IP amphetamine (2 mgikg), dopamine (DA) in dialysate from the accumbens increased from a baseline of 3 pg/20 ~1 to I I pg/20 yl; whereas dopamine metabolites. DOPAC and HVA decreased. This was probably due to block of DA reuptake and inhibition of monoamine oxidase, MAO. Accumbens serotonin increased from a baseline of 8 to 11 pg/ZO ~1. Changes in the ventral striatum were similar. In the second experiment, microdialysis was performed before and after local injection of amphetamine (4 pg) to reveal effects of
Brain Research, 1999
Ž . Brain microdialysis coupled to high performance liquid chromatography with electrochemical de... more Ž . Brain microdialysis coupled to high performance liquid chromatography with electrochemical detection HPLC-ED was used to Ž . Ž . evaluate the influence of melatonin on extracellular concentration of acetylcholine ACh in the nucleus accumbens NAc of rats. Motor activity was simultaneously monitored during the dialysis sessions with an activity meter. Melatonin and prazosin were administered Ž . locally through the dialysis probe. It was found that melatonin dose-dependently increased accumbens ACh. Melatonin 3 mM decreased Ž . horizontal activity and increased vertical activity, while another dose 100 mM enhanced both horizontal and vertical activity. Prazosin, a putative melatonin antagonist, blocked the effects of melatonin on both motor activity and ACh release when given 20 min before melatonin. Overall, these results suggest that melatonin modulates the release of ACh in the NAc and the pattern of motor activity in the rat. q
Brain Research, 2000
dopaminergic activity in the nucleus accumbens (NAC). In the present set of experiments, microdia... more dopaminergic activity in the nucleus accumbens (NAC). In the present set of experiments, microdialysis probes were implanted in the NAC, and glutamate, g-aminobutyric acid (GABA) and dopamine (DA) were measured during electrical stimulation of the MPFC, after coronal transection caudal to the MPFC and after a systemic injection of amphetamine in transected rats. Electrical stimulation of the MPFC caused a transient enhancement of glutamate release in the NAC, no change in GABA levels and a long lasting increase in DA levels. Medial prefrontal transection did not change basal glutamate or GABA levels in the NAC, but increased basal DA levels. Amphetamine administration decreased GABA levels in medial prefrontal transected rats, had no effect on glutamate and increased DA levels more than in controls. The experiments suggest that glutamatergic activity in the accumbens decreases dopamine release. Medial prefrontal transection reduces glutamatergic tone and enhances dopamine release, which probably decreases GABAergic activity in the NAC. Presumably, GABA inhibition in the NAC enhances social interaction.
Alcohol, 1992
acts in the brain to reduce ethanol toxicity in rats. ALCOHOL 9(6) 519-522, 1992.-Although for ma... more acts in the brain to reduce ethanol toxicity in rats. ALCOHOL 9(6) 519-522, 1992.-Although for many years it has been proposed that megadoses of pyridoxine protect from ethanol toxicity, this issue remains unclear. In the present report the interaction between ethanol and pyridoxine was tested. Pyridoxine was administered intramuscularly or intracerebroventricularly to rats. Intramuscular administration of 187.2 mg/kg of pyridoxine displaced the ethanol-lethality dose curve significantly toward the right (p < 0.005) and increased the LDso of ethanol from 4.46 to 5.19 g/kg (p < 0.005). Intracerebroventricular administration of pyridoxine (1.1 mg) completely suppressed the mortality due to a LD~00 of ethanol and the effect was dose dependent. We conclude that pyridoxine is an effective treatment for ethanol intoxication. The results are discussed in terms of an interaction of ethanol and pyridoxine on the GABAergic system.
Pharmacology Biochemistry and Behavior, 1989
Daily rhythms in extracellular levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-... more Daily rhythms in extracellular levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were examined in the region of the paraventricular nucleus (PVN), using intracerebral microdialysis combined with high performance liquid chromatography and electrochemical detection. Samples of PVN dialysate, from 11 rats on a 12/12 hr light/dark cycle, were collected and assayed for 5-HIAA every 2 hr for 3 days. During the first 2 days the rats were given free access to food. During the 3rd day they were deprived of food for a 24-hr period and then given food for 4 hr. The results showed that in freely-feeding rats, there was a 24-hr rhythm in the levels of 5-HIAA, with a marked transient peak just after the beginning of the dark portion of the light/dark cycle and stable levels at all other times. When the animals were food-deprived, PVN levels of this metabolite remained stable, and the early dark peak was abolished, suggesting that it might have been consequent to the eating behavior which normally occurred at this time. In the 4-hr refeeding period, there were no changes in 5-HIAA levels, despite the intense eating behavior which occurred during this time. These patterns of 5-HIAA in the PVN region, taken together with previous evidence, suggest that PVN serotonin metabolism may increase in association with feeding specifically in the early portion of the nocturnal eating period, when it may play a role in controlling food intake and macronutrient selection.
Pharmacology Biochemistry and Behavior, 1987
BAPTISTA, T , M PARADA AND L HERNANDEZ Long term admmtstratton of some anttpsychottc drugs mcreas... more BAPTISTA, T , M PARADA AND L HERNANDEZ Long term admmtstratton of some anttpsychottc drugs mcreases body wetght and feeding in rats Are D2 dopamme receptors tnvolved~ PHARMACOL BIOCHEM BEHAV 27(3) 399-405, 1987 --Long term admlmstratlon of the antlpsychoUc drugs tluondazlne, tnfluoperazme, hatopendol, and sulpmde mcreased body weight m rats Th~s effect was found to be sex dependent, that is, while female rats were prone to gain weight, male rats did not Chlorpromazme and fluphenazme decreased body weight m male rats but did not affect females The mechamsm of body wetght gain was mvesttgated w~th sulpmde A hnear relatmnshlp between dose of sulpmde and body weight gain was found Also, sulpmde increased caloric retake, and both actions were counteracted by bromocnptme, a spectfic D2 receptor agomst These results confirm that antlpsychotlc drugs affect feeding and body weight and suggest that hyperphagla and body weight gain might be medmted by blockade of dopamlne receptors of the D2 type Antlpsychotlc drugs Bromocnptme Body weight Feeding Dopamlne D2 receptors
Pharmacology, 1978
Phenylpropanolamine hydrochloride (PPA) is a widely used decongestant and anorectic drug. The pre... more Phenylpropanolamine hydrochloride (PPA) is a widely used decongestant and anorectic drug. The present study investigated the hypoglycemic effects of intraperitoneal PPA on rats to test the possibility that it might derive some of its anorectic properties through effects on glucostatic mechanisms. PPA tended to lower blood glucose levels in normal rats; the glycemia reducing effect was larger and statistically significant in rats made hyperglycemic by prior treatment with streptozocin to cause diabetes. This is the first evidence that PPA migh possibly reduce feeding by increasing blood sugar utilization.
Psychopharmacology, 1991
Cocaine and two other local anesthetics were applied directly into the nucleus accumbens for 20 m... more Cocaine and two other local anesthetics were applied directly into the nucleus accumbens for 20 min by diffusion from a 4 mm microdialysis probe in freely moving rats. Cocaine (7.3 mM) increased the extracellular concentration of dopamine (DA). Equimolar procaine did also, but was not as potent as cocaine. Equimolar lidocaine had no effect. The concentration of these drugs outside the probe as measured by capillary electrophoresis in vitro was about 28% of that inside the probe, i.e. 72% remained inside. However, an in vivo test showed that about 53% cocaine and procaine, and 37% lidocaine remained in the perfusion fluid after passing through a probe inserted in the brain. This suggests that in vivo about 68 nmol cocaine diffused into the nucleus accumbens (NAC) during the 20 min. Five conclusions are drawn: (1) this confirms our earlier finding that local injection of cocaine increases extracellular DA, but in this case the cocaine was infused via the probe without disturbing the animal; (2) the action of cocaine on dopamine terminals in the accumbens is independent of local anesthesia; (3) procaine may enhance mood by a cocaine-like effect; (4) capillary electrophoresis has potential for measuring cocaine levels in small samples and (5) in vitro calibrations are of limited value to evaluate in vivo performance of microdialysis probes.
Brain Research Bulletin, 1990
Fluctuations of cortical dopamine during feeding were examined by in vivo microdialysis. Dopamine... more Fluctuations of cortical dopamine during feeding were examined by in vivo microdialysis. Dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured by high performance liquid chromatography and electrochemical detection. Food-deprived rats were trained to eat by pressing a bar for food when a light and a feeder were turned on. The day of the experiment a microdialysis probe was inserted in the prefrontal cortex (PFC) of the rats and dialysates were collected every 20 minutes while the light and the feeder were off. When the neurochemical baseline was stable the light and the feeder were turned on for 20 minutes only. During this time the rats ate (mean 204 pellets = 9.2 g) and DA increased about 55%, remained high for another 20 minutes and then gradually returned toward baseline levels. DOPAC increased 30% in the first 20 minutes after the eating bout. HVA increased 40 minutes after the eating bout. Histology showed the probes were located in the anteromedial region of the PFC. We conclude that dopamine turnover in the mesocortical system increases during feeding under the conditions used. The results are discussed in terms of the role of the PFC in food intake modulation.
Brain Research Bulletin, 1994
TUCCI, S., R. FERNANDEZ, T. BAPTISTA, E. MURZI AND L. HERNANDEZ. Dopamine increase in rhe prefron... more TUCCI, S., R. FERNANDEZ, T. BAPTISTA, E. MURZI AND L. HERNANDEZ. Dopamine increase in rhe prefrontal cortex correlates with reversal of haloperidol-induced catalepsy in rats. BRAIN RES BULL 35(2) 125-133, 1994.-The mechanism by which forced swimming reverses haloperidol-induced catalepsy was examined by measuring dopamine (DA) turnover in the nucleus accumbens-ventromedial caudate (NAC-C) and the prefrontal cortex (PFC) in rats. DA and its metabolites 3,4-dihydroxiphenylacetic acid (DOPAC) and homovanillic acid (HVA) were assessed by microdialysis and high pressure liquid chromatography with electrochemical detection (HPLC-ED) after systemic administration of a cataleptic dose of haloperidol (5 mg/kg) or saline. Haloperidol-induced catalepsy was temporarily suppressed by forced swimming. Haloperidol-treated rats showed an increase of DA, DOPAC, and HVA overflow in the PFC and the NAC-C. This increase was greater in the PFC of rats that were forced to swim. Rats that were not treated with haloperidol but were forced to swim (control group) showed an increase of DA, DOPAC, and HVA in the PFC but not in the NAC-C. Zero micrograms, 5 pg, 10 pg. and 20 pg of DA was bilaterally injected in the PFC of cataleptic rats to evaluate the hypothesis that DA in the PFC reverses catalepsy. Haloperidol-induced catalepsy was diminished by bilateral microinjections of IO pg and 20 pg but not by 5 pg of DA in the PFC. The higher the dose of DA, the longer the decrease of catalepsy. These results suggest that an increase of DA turnover in the PFC might mediate temporal suppression of haloperidol-induced catalepsy. The mechanism by which the mesocortical DA system reduces catalepsy is discussed.
Brain Research, 1989
Microdialysis was used to monitor serotonin, 5-hydroxyindoleacetic acid (5-HIAA) and the metaboli... more Microdialysis was used to monitor serotonin, 5-hydroxyindoleacetic acid (5-HIAA) and the metabolites of dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the perifornical lateral hypothalamus (PFH) of freely moving rats. Systemically administered d-fenfluramine (d-FEN) increased extracellular serotonin, DOPAC and HVA, while decreasing serotonin&amp;#39;s metabolite 5-HIAA. Local application of d-FEN directly to the hypothalamic terminal region caused large increases in extracellular serotonin and had a tendency to decrease all 3 metabolites. This effect was confirmed when d-FEN was infused locally by reverse dialysis. These results provide direct evidence that the anorectic drug d-FEN can increase extracellular serotonin in the hypothalamus in vivo and suggest a serotonergic action in the perifornical region. This finding is consistent with our report that a meal also increases serotonin in this region.
Brain Research, 1982
Earlier research from this laboratory showed that 6-hydroxydopamine (6-OHDA) injected into the ve... more Earlier research from this laboratory showed that 6-hydroxydopamine (6-OHDA) injected into the ventral midbrain of rats causes overeating and the gradual development of obesity in association with extensive depletion of forebrain norepinephrine. It was proposed that depletion of norepinephrine or epinephrine was the cause of the behavioral abnormality. This was questioned on the basis of experiments showing that 6-OHDA can cause non-selective lesions and also that non-selective neurotoxins can cause hyperphagia. To help resolve this question, the present experiments used 191 rats in 28 groups to test 3 doses of 6-OHDA and 3 different pretreatments with reuptake blockers, amphetamine, desmethylimipramine and benztropine. The result of midbrain 6-OHDA alone was hyperphagia that was highly correlated with the dose. Pretreatment with intraperitoneal desmethylimipramine (DMI) caused gastric distress, and systemic amphetamine caused delayed overeating, but these unwanted side effects were avoided by injecting the drugs directly into the midbrain 15 min before the 6-OHDA. DMI and amphetamine partially prevented catecholamine depletion in the forebrain and totally prevented subsequent hyperphagia and obesity. Benztropine prevented dopamine depletion, but had no effect on hyperphagia. We conclude that some of the neurons protected by local injection of amphetamine and DMI are probably norepinephrine or epinephrine fibers that ascend through the ventral midbrain and have as one of their functions the inhibition of food intake. These neurons could also play a role in the control of body weight.
Pharmacology Biochemistry and Behavior, 1989
Daily rhythms in extracellular levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-... more Daily rhythms in extracellular levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were examined in the region of the paraventricular nucleus (PVN), using intracerebral microdialysis combined with high performance liquid chromatography and electrochemical detection. Samples of PVN dialysate, from 11 rats on a 12/12 hr light/dark cycle, were collected and assayed for 5-HIAA every 2 hr for 3 days. During the first 2 days the rats were given free access to food. During the 3rd day they were deprived of food for a 24-hr period and then given food for 4 hr. The results showed that in freely-feeding rats, there was a 24-hr rhythm in the levels of 5-HIAA, with a marked transient peak just after the beginning of the dark portion of the light/dark cycle and stable levels at all other times. When the animals were food-deprived, PVN levels of this metabolite remained stable, and the early dark peak was abolished, suggesting that it might have been consequent to the eating behavior which normally occurred at this time. In the 4-hr refeeding period, there were no changes in 5-HIAA levels, despite the intense eating behavior which occurred during this time. These patterns of 5-HIAA in the PVN region, taken together with previous evidence, suggest that PVN serotonin metabolism may increase in association with feeding specifically in the early portion of the nocturnal eating period, when it may play a role in controlling food intake and macronutrient selection.
Pharmacology Biochemistry and Behavior, 1987
BAPTISTA, T , M PARADA AND L HERNANDEZ Long term admmtstratton of some anttpsychottc drugs mcreas... more BAPTISTA, T , M PARADA AND L HERNANDEZ Long term admmtstratton of some anttpsychottc drugs mcreases body wetght and feeding in rats Are D2 dopamme receptors tnvolved~ PHARMACOL BIOCHEM BEHAV 27(3) 399-405, 1987 --Long term admlmstratlon of the antlpsychoUc drugs tluondazlne, tnfluoperazme, hatopendol, and sulpmde mcreased body weight m rats Th~s effect was found to be sex dependent, that is, while female rats were prone to gain weight, male rats did not Chlorpromazme and fluphenazme decreased body weight m male rats but did not affect females The mechamsm of body wetght gain was mvesttgated w~th sulpmde A hnear relatmnshlp between dose of sulpmde and body weight gain was found Also, sulpmde increased caloric retake, and both actions were counteracted by bromocnptme, a spectfic D2 receptor agomst These results confirm that antlpsychotlc drugs affect feeding and body weight and suggest that hyperphagla and body weight gain might be medmted by blockade of dopamlne receptors of the D2 type Antlpsychotlc drugs Bromocnptme Body weight Feeding Dopamlne D2 receptors
Pharmacology, 1978
Phenylpropanolamine hydrochloride (PPA) is a widely used decongestant and anorectic drug. The pre... more Phenylpropanolamine hydrochloride (PPA) is a widely used decongestant and anorectic drug. The present study investigated the hypoglycemic effects of intraperitoneal PPA on rats to test the possibility that it might derive some of its anorectic properties through effects on glucostatic mechanisms. PPA tended to lower blood glucose levels in normal rats; the glycemia reducing effect was larger and statistically significant in rats made hyperglycemic by prior treatment with streptozocin to cause diabetes. This is the first evidence that PPA migh possibly reduce feeding by increasing blood sugar utilization.
Brain Research Bulletin, 1990
In the present experiments we extend previous findings that established a relationship between fe... more In the present experiments we extend previous findings that established a relationship between feeding behavior and hypothalamic serotonin as measured by in vivo microdialysis. The new result is hypothalamic release of serotonin in anticipation of eating when the animal sees and smells food. We have now verified brain serotonin peaks in four different ways: 1) a serotonergic reuptake blocker (fluoxetine 1 or 10 μM) in the perfusion medium raised basal levels of serotonin.2) every sample was oxidized at two potentials using a dual potentiostat to confirm the voltage characteristics of each peak.3) serotonin peaks were reduced by the selective serotonin cell body agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), thus helping confirm that most of the serotonin observed in these experiments was neuronal in origin, and 4) lateral and medial hypothalamic microdialysis probes were used simultaneously to monitor the degree of diffusion from one to the other. The results show that extracellular serotonin increases at both sites during preingestive events as well as during eating, but not afterwards.
Annals of The New York Academy of Sciences, 1989
To help understand the neurochemical basis of behavior reinforcement, we have perfected the techn... more To help understand the neurochemical basis of behavior reinforcement, we have perfected the technique of in vivo microdialysis for studying brain functions in behaving animals. Monoamines and their main metabolites were sampled in the extracellular space of the hypothalamus or nucleus accumbens in rats given food, water, salt, anorectic drugs, conditioned taste aversion, or addictive psychomotor stimulants. This has contributed to the view that in the paraventricular nucleus (PVN) norepinephrine facilitates feeding and serotonin inhibits it; in the perifornical lateral hypothalamus (PFH), the monoamines contribute to inhibition of feeding; and in the nucleus accumbens (NAC), dopamine facilitates positive reinforcement. Microdialysis results are summarized in the last paragraph. To put the new results in the context of eating disorders, we begin with a review of earlier monoamine depletion and injection studies.
Psychopharmacology, 1983
Rats learned to self-administer d-amphetamine (10 μg/μl) through a cannula implanted in the nucle... more Rats learned to self-administer d-amphetamine (10 μg/μl) through a cannula implanted in the nucleus accumbens. They responded more frequently for 65±15 nl of amphetamine than for equal amounts of saline. When presented with two levers (one amphetamine, one blank) they responded more on the correct lever for amphetamine. They would also switch levers, when necessary, to maintain access to the drug. When half the usual drug intake was given automatically, animals reduced their response rate by half, thus self-regulating the total amount of amphetamine they received. In tests for leakage into the ventricles, eight rats that self-injected with an accumbens cannula showed response extinction when switched to a ventricular cannula. We conclude that amphetamine self-injected into the accumbens is a positive reinforcer. This localization of ‘amphetamine reward’ suggests that the nucleus accumbens contains a synaptic mechanism underlying amphetamine abuse and, perhaps, also natural reinforcement of behavior.
Brain Research Bulletin, 1987
~rt/rn,7c,r,rr.s tr7ic,rcrclicr/~sis and crmphctcminr, injbsion in the nw/~~~s crc~c~rcmhor.s and... more ~rt/rn,7c,r,rr.s tr7ic,rcrclicr/~sis and crmphctcminr, injbsion in the nw/~~~s crc~c~rcmhor.s and striatrrm c!ffrz~!\: mo~+ng rats: Inc~rcwsc~ i/l r.utrrrc~c~//rt/nr doprrrxitle rrnd serofotzin. BRAIN RES BULL 19(6f 623-628, 1987.-To test the effects of systemic and local amphetamine on dopamine and serotonin release in freely moving rats, guide cannulas were implanted in the nucleus accumbens and ventral striatum for removable 200 i* microdialysis probes. Comparing 4.5 min samples before and after IP amphetamine (2 mgikg), dopamine (DA) in dialysate from the accumbens increased from a baseline of 3 pg/20 ~1 to I I pg/20 yl; whereas dopamine metabolites. DOPAC and HVA decreased. This was probably due to block of DA reuptake and inhibition of monoamine oxidase, MAO. Accumbens serotonin increased from a baseline of 8 to 11 pg/ZO ~1. Changes in the ventral striatum were similar. In the second experiment, microdialysis was performed before and after local injection of amphetamine (4 pg) to reveal effects of
Brain Research, 1999
Ž . Brain microdialysis coupled to high performance liquid chromatography with electrochemical de... more Ž . Brain microdialysis coupled to high performance liquid chromatography with electrochemical detection HPLC-ED was used to Ž . Ž . evaluate the influence of melatonin on extracellular concentration of acetylcholine ACh in the nucleus accumbens NAc of rats. Motor activity was simultaneously monitored during the dialysis sessions with an activity meter. Melatonin and prazosin were administered Ž . locally through the dialysis probe. It was found that melatonin dose-dependently increased accumbens ACh. Melatonin 3 mM decreased Ž . horizontal activity and increased vertical activity, while another dose 100 mM enhanced both horizontal and vertical activity. Prazosin, a putative melatonin antagonist, blocked the effects of melatonin on both motor activity and ACh release when given 20 min before melatonin. Overall, these results suggest that melatonin modulates the release of ACh in the NAc and the pattern of motor activity in the rat. q
Brain Research, 2000
dopaminergic activity in the nucleus accumbens (NAC). In the present set of experiments, microdia... more dopaminergic activity in the nucleus accumbens (NAC). In the present set of experiments, microdialysis probes were implanted in the NAC, and glutamate, g-aminobutyric acid (GABA) and dopamine (DA) were measured during electrical stimulation of the MPFC, after coronal transection caudal to the MPFC and after a systemic injection of amphetamine in transected rats. Electrical stimulation of the MPFC caused a transient enhancement of glutamate release in the NAC, no change in GABA levels and a long lasting increase in DA levels. Medial prefrontal transection did not change basal glutamate or GABA levels in the NAC, but increased basal DA levels. Amphetamine administration decreased GABA levels in medial prefrontal transected rats, had no effect on glutamate and increased DA levels more than in controls. The experiments suggest that glutamatergic activity in the accumbens decreases dopamine release. Medial prefrontal transection reduces glutamatergic tone and enhances dopamine release, which probably decreases GABAergic activity in the NAC. Presumably, GABA inhibition in the NAC enhances social interaction.
Alcohol, 1992
acts in the brain to reduce ethanol toxicity in rats. ALCOHOL 9(6) 519-522, 1992.-Although for ma... more acts in the brain to reduce ethanol toxicity in rats. ALCOHOL 9(6) 519-522, 1992.-Although for many years it has been proposed that megadoses of pyridoxine protect from ethanol toxicity, this issue remains unclear. In the present report the interaction between ethanol and pyridoxine was tested. Pyridoxine was administered intramuscularly or intracerebroventricularly to rats. Intramuscular administration of 187.2 mg/kg of pyridoxine displaced the ethanol-lethality dose curve significantly toward the right (p < 0.005) and increased the LDso of ethanol from 4.46 to 5.19 g/kg (p < 0.005). Intracerebroventricular administration of pyridoxine (1.1 mg) completely suppressed the mortality due to a LD~00 of ethanol and the effect was dose dependent. We conclude that pyridoxine is an effective treatment for ethanol intoxication. The results are discussed in terms of an interaction of ethanol and pyridoxine on the GABAergic system.
Pharmacology Biochemistry and Behavior, 1989
Daily rhythms in extracellular levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-... more Daily rhythms in extracellular levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were examined in the region of the paraventricular nucleus (PVN), using intracerebral microdialysis combined with high performance liquid chromatography and electrochemical detection. Samples of PVN dialysate, from 11 rats on a 12/12 hr light/dark cycle, were collected and assayed for 5-HIAA every 2 hr for 3 days. During the first 2 days the rats were given free access to food. During the 3rd day they were deprived of food for a 24-hr period and then given food for 4 hr. The results showed that in freely-feeding rats, there was a 24-hr rhythm in the levels of 5-HIAA, with a marked transient peak just after the beginning of the dark portion of the light/dark cycle and stable levels at all other times. When the animals were food-deprived, PVN levels of this metabolite remained stable, and the early dark peak was abolished, suggesting that it might have been consequent to the eating behavior which normally occurred at this time. In the 4-hr refeeding period, there were no changes in 5-HIAA levels, despite the intense eating behavior which occurred during this time. These patterns of 5-HIAA in the PVN region, taken together with previous evidence, suggest that PVN serotonin metabolism may increase in association with feeding specifically in the early portion of the nocturnal eating period, when it may play a role in controlling food intake and macronutrient selection.
Pharmacology Biochemistry and Behavior, 1987
BAPTISTA, T , M PARADA AND L HERNANDEZ Long term admmtstratton of some anttpsychottc drugs mcreas... more BAPTISTA, T , M PARADA AND L HERNANDEZ Long term admmtstratton of some anttpsychottc drugs mcreases body wetght and feeding in rats Are D2 dopamme receptors tnvolved~ PHARMACOL BIOCHEM BEHAV 27(3) 399-405, 1987 --Long term admlmstratlon of the antlpsychoUc drugs tluondazlne, tnfluoperazme, hatopendol, and sulpmde mcreased body weight m rats Th~s effect was found to be sex dependent, that is, while female rats were prone to gain weight, male rats did not Chlorpromazme and fluphenazme decreased body weight m male rats but did not affect females The mechamsm of body wetght gain was mvesttgated w~th sulpmde A hnear relatmnshlp between dose of sulpmde and body weight gain was found Also, sulpmde increased caloric retake, and both actions were counteracted by bromocnptme, a spectfic D2 receptor agomst These results confirm that antlpsychotlc drugs affect feeding and body weight and suggest that hyperphagla and body weight gain might be medmted by blockade of dopamlne receptors of the D2 type Antlpsychotlc drugs Bromocnptme Body weight Feeding Dopamlne D2 receptors
Pharmacology, 1978
Phenylpropanolamine hydrochloride (PPA) is a widely used decongestant and anorectic drug. The pre... more Phenylpropanolamine hydrochloride (PPA) is a widely used decongestant and anorectic drug. The present study investigated the hypoglycemic effects of intraperitoneal PPA on rats to test the possibility that it might derive some of its anorectic properties through effects on glucostatic mechanisms. PPA tended to lower blood glucose levels in normal rats; the glycemia reducing effect was larger and statistically significant in rats made hyperglycemic by prior treatment with streptozocin to cause diabetes. This is the first evidence that PPA migh possibly reduce feeding by increasing blood sugar utilization.