Noradrenergic system: Effect of DSP4 and FLA-57 on ethanol intake in ethanol preferring rats (original) (raw)
Related papers
Drug and Alcohol Dependence, 1988
Male rats were treated with one ethanol (2.0 g/kg i.p.) or saline injections once a week for 50 weeks. During this treatment period the rats had in addition access to ethanol (10% in drinking fluid) as a choice against water for 24 h prior to the injection. During the following evaluation period, animals had a continuous choice between ethanol and water and the concentration of the ethanol solution increased every 3rd week from 5 to 10, 15 and 25%, with 10% as a reference tested between the other concentrations. The animals were killed after an abstinence of 4 weeks, whereupon the concentrations of noradrenaline (NA), dopamine (DA), serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) were determined in the frontal cortex. In the remaining cerebral cortex, activity of monoamine oxidase, reuptake of NA and stimulated inositol phospholipid (PI) breakdown was also determined. Muscarinic binding sites were determined in the striatum. During treatment, saline injected rats had a constant voluntary 24 h ethanol intake. There was a decrease in the corresponding intake in the animals given the ethanol injections. The diminishing of the intake was more marked in rats starting treatment at an age of 19.4 weeks when compared to rats starting at an age of 5.4 weeks. In the evaluation period the ethanol intake was fairly constant for all groups. However, the regressions between intake of the reference concentration when plotted against the different tested concentrations were most marked in the group where ethanol injections started at an early age. In the total material there were significant F-values when concentrations of NA, 5-HIAA, 5-HT/5-HIAA in the cortex and muscarinic binding sites in the striatum were tested. Age could not be excluded as a contributing factor, but for muscarinic binding sites in the striatum, concentrations of DA and 5-HIAA in the cortex, and potassium stimulated PI breakdown in the cortex significant regressions with voluntary ethanol intake as dependent variable could be established. Since these intakes are stable, a causal relation with dependence may be involved.
Ethanol and dopaminergic systems
Pharmacology Biochemistry and Behavior, 1983
Chronic ethanol consumption produces derangements of cell membrane structure, perhaps by changing membrane lipid content. This impairment leads to modification of membrane-related processes. In fact, after chronic ethanol exposure, an increase in striatal adenylate-cyclase activity occurs. On the other hand, dopamine is unable to further potentiate the production of cyclic AMP. This finding demonstrates that the dopaminergic receptor associated with adenylate-cyclase activity is affected by chronic ethanol treatment. In particular, the affinity of the dopaminergic receptor labelled by 3H-Spiperone is enhanced. In addition, the receptor-adenylate cyclase coupling system is impaired after chronic in vivo exposure of animals to ethanol. Ethanol Striatal dopaminergic systems Dopamine receptors Adenylate cyclase Guanyl nucleotides
Effects of chronic ethanol intake at a low dose on the rat brain dopaminergic system
Alcohol, 1993
Effects of chronic ethanol intake at a low dose on the rat brain dopaminergic system. ALCOHOL 10(1) 45-49, 1993.-The effects of 8-week ethanol treatment (3% v/v in drinking water) on the rat brain dopaminergic system were investigated. Chronic ethanol consumption induced a significant increase in the number of dopamine Dt receptor sites in the caudate putamen. Conversely, no significant changes were observed in D2 receptor density or affinity. Biochemical results were in agreement with behavioral data, as amphetamine-induced locomotor hyperactivity was significantly higher in ethanol-treated rats in comparison to controls. Moreover, grooming behavior in response to SKF 38393, a selective agonist of DI receptors was potentiated in ethanol-treated rats, whereas locomotor hyperactivity induced by LY 171555 (a selective agonist of D 2 receptors) was not affected by ethanol treatment. The results indicate that changes in dopamine receptors may occur in the central nervous system at levels of ethanol intake that do not induce tolerance or dependence.
Alcoholism-clinical and Experimental Research, 1998
Neuropeptide Y (NPY) is a hexatriacontapeptide amide that is now well characterized as a neuromodulator in the central nervous system (CNS). When infused into the CNS, NPY produces both anxiolytic and orexigenic effects. NPY's anxiolytic effects appear to be mediated through receptors in the central amygdala, whereas its orexigenic effects are localized in discrete hypothalamic nuclei. Both food restriction and food deprivation produce increased levels of the pep-tide in the hypothalamus that are ameliorated by refeeding. However, the effects of alcohol consumption/deprivation on NPY levels remain unknown. The present study sought to determine if brain NPY levels were affected by either alcohol exposure and/or correlated with genetic differences in preference for drinking alcohol. In the first experiment, NPY-like immunoreactivity (NPY-LI) was compared in alcohol-naive, alcohol-preferring (P), and nonpreferring (NP) rats. After tissue extraction, NPY-LI was measured by radioimmunoassay: amygdala, hippocampus, frontal cortex, hypothalamus, and caudate. P rats were found to have significantly lower NPY-LI in amygdala (F= 4.69, p 0.04), hippocampus (F= 7.03, p < 0.01), and frontal cortex (F= 4.7, p < 0.04), compared with NP rats. In the second experiment, heterozygous Wistar rats were exposed to alcohol for 14 hr/day for 7 weeks in alcohol vapor chambers (mean blood alcohol concentrations =180 mg%) or control chambers. At 7 weeks of alcohol exposure, no significant changes in NPY-LI in were found. At 1 month after ethanol withdrawal, however, the ethanol-exposed animals had significantly higher NPY-LI in the hypothalamus (F= 4.78, p < 0.04) when compared with the nonexposed controls. Taken together, these studies suggest that exposure to chronic ethanol may affect NPY-LI at the level of the hypothalamus in a fashion similar to food restriction, because 4 weeks after alcohol withdrawal, significantly higher NPY levels are found. In addition, differences in NPY-LI in limbic areas and frontal cortex between alcohol-naive P and NP rats suggest that NPY may also play a role in risk for the development of alcohol preference either by modulating the “tension-reduction” properties of alcohol or by influencing consummatory behaviors.
Psychopharmacology, 1994
Previous work has reported that the 5-hydroxytryptamine (5-HT)I A agonist, 8-hydroxy 2-(di-n-propylamino)tetralin (8-OH DPAT), reduces ethanol intake by rats. However, as 8-OH DPAT reduces 5-HT neurotransmission, these findings are inconsistent with the proposed inhibitory role of central 5-HT neurons on ethanol intake. We examined the effect of 8-OH DPAT on ethanol, water and food intake in rats maintained on a limited access schedule using a lower dose range (6-250 gg/kg) and by assessing concomitant changes in behaviour. Low doses of 8-OH DPAT enhanced ethanol intake even when food and water were offered as alternatives. Suppression in ethanol intake was observed at higher doses where elements of the 5-HT syndrome were apparent. Similar observations were made in both fluid and nonfluid deprived water drinking rats, suggesting the latter effect is non-selective. Therefore 8-OH DPAT may both increase or decrease ethanol consumption in the rat depending on the dose used.
Effects of a range of dopamine receptor agonists and antagonists on ethanol intake in the rat
European Journal of Pharmacology, 1996
The aim of this study was to assess the effects of a range of dopaminergic agents on consumption of an ethanol solution ( 10% ethanol, 3% glucose) in rats. A two-bottle, free-choice paradigm was used following induction of ethanol consumption and preference in standard laboratory rats. The model used provides a robust and reliable level of ethanol oral administration in normal laboratory rats. Both ethanol intake and preference were reduced by a dopamine D~ receptor partial agonist, SFK 38393 ((+)-l-phenyl-2,3,4,5-tetrahydro-(l H)-3-benzazepine-7,8-diol hydrochloride), in a dose-dependent manner. The dopamine D2/D 3 receptor agonist 7-OH-DPAT ((+)-7-hydroxy-N,N-(di-n-propyl-2-aminotetralin)) at the lowest dose of 0.01 mg/kg increased both ethanol intake and preference. At higher doses (0.03-0.1 mg/kg) no significant effects were found. The dopamine D I receptor antagonist SCH 23390 (R-( + )-7-chloro-2,3,4,5-tetrahydro-3-methyl-l-phenyl-lH-3-benzazepine-8-ol), dopamine D2/D 3 receptor antagonist raclopride and 5-HT2/D 2 receptor antagonist risperidone did not affect ethanol consumption, although all at high doses induced a significant decrease in water intake, indicating a non-specific decrease in consummatory behavior with these compounds. These results suggest the involvement of the dopaminergic system in ethanol intake and ethanol reinforcement with dopamine D~ and D2/D ? receptors playing opposing roles. Blockade of dopamine D 2 receptors had no selective effect on ethanol consumption and ethanol preference.