K. Eberle-Wang - Academia.edu (original) (raw)

Papers by K. Eberle-Wang

Research paper thumbnail of Peripherally administered alpha-methyl-5-hydroxy-tryptamine and 5-carboxamidotryptamine reduce food intake via different mechanisms in rats

Behavioural pharmacology, 1989

Peripherally administering the serotonin (5-HT) analogs, alpha-methyl-5-hydroxytryptamine (alpha-... more Peripherally administering the serotonin (5-HT) analogs, alpha-methyl-5-hydroxytryptamine (alpha-Me-5-HT) and 5-carboxamidotryptamine (5-CT), reduced milk consumption by food-deprived rats. 5-CT decreased milk intake 100-fold more potently than alpha-Me-5-HT (ID(50)'s =.06 and 5.6µmol/kg, respectively). 5-CT also elicited drinking but alpha-Me-5-HT did not. The nonselective 5-HT antagonist, methysergide, blocked the anorectic actions of each agonist. By contrast, the 5-HT(2) antagonist, ketanserin, and the peripheral 5-HT(2) antagonist, xylamidine, only prevented anorexia due to alpha-Me-5-HT. These results suggest that stimulating either peripheral 5-HT(2) or peripheral 5-HT(1)-like receptors inhibits feeding in rats. 5-HT(1)-like sites may also mediate 5-HT-induced drinking.

Research paper thumbnail of Serotonin contracts the isolated rat pylorus via a 5-HT2-like receptor

The American journal of physiology, 1994

Serotonin (5-HT) produced concentration-dependent contractions of the isolated rat pylorus in vit... more Serotonin (5-HT) produced concentration-dependent contractions of the isolated rat pylorus in vitro. Serotonergic contractions were antagonized by the calcium L-channel blocker, diltiazem, but not by tetrodotoxin or atropine. Three drugs that block 5-HT2 receptors, ketanserin, xylamidine, and methysergide, unsurmountably inhibited contractions to 5-HT. In contrast, antagonists of 5-HT3, 5-HT1A/1B, beta-adrenergic, or alpha 1-adrenergic receptors did not alter the response to 5-HT. Devazepide, an antagonist of cholecystokinin (CCK) type-A receptors, blocked contraction produced by CCK-8 but not by 5-HT. Conversely, the 5-HT2 antagonists did not affect CCK-stimulated contraction. These results suggest that 5-HT contracts the pylorus by a 5-HT2-like receptor on muscle and that this response occurs independently of CCKergic receptor mechanisms. Furthermore, the parallel between the overall pharmacological profile for serotonergic contraction of the pylorus and that observed previously f...

Research paper thumbnail of Abdominal vagotomy dissociates the anorectic mechanisms for peripheral serotonin and cholecystokinin

The American journal of physiology, 1993

These studies compared the effects of total abdominal vagotomy (VGX) on ingestive actions produce... more These studies compared the effects of total abdominal vagotomy (VGX) on ingestive actions produced by peripheral serotonergic and cholecystokinergic (CCKergic) stimulation in rats. Subcutaneous injection of 0.01-0.16 mumol/kg of the serotonin (5-HT) analogue 5-carboxamidotryptamine (5-CT) dose-dependently reduced mash intake equally in VGX rats and their laparotomized (LAP) controls but concurrently stimulated drinking only in the controls. The sulfated octapeptide of cholecystokinin (CCK-8, 4.0 nmol/kg ip) also reduced food intake only in the controls. In a second set of rats, vagotomy did not alter anorexia after intraperitoneal administration of either 2.0 or 8.0 mumol/kg of 5-HT or of 0.03 mumol/kg of 5-CT but abolished anorexia after a large dose of CCK-8 (8.0 nmol/kg). The completeness of vagotomy was verified histologically by immunohistochemical staining of the vagal bundles for the high molecular weight form of neurofilament-H protein. We report for the first time that 5-CT...

Research paper thumbnail of The CCK-A receptor antagonist, devazepide, blocks the anorectic action of CCK but not peripheral serotonin in rats

Pharmacology Biochemistry and Behavior, 1992

The CCK-A receptor antagonist, devazepide, blocks the anorectic action of CCK but not peripheral ... more The CCK-A receptor antagonist, devazepide, blocks the anorectic action of CCK but not peripheral serotonin in rats. PHARMACOL BIOCHEM BEHAV 43(3), 943-947, 1992.-A role has been proposed for cholecystokinin (CCK)-A-type receptors in mediating the anorectic action produced by serotonergic stimulation in rats. We examined the effect of pretreatment with the CCK-A antagonist devazepide (DVZ) on anorexia produced by peripheral administration of serotonin [5-hydroxytryptamine (5-HT)] or CCK-8 in 3-h food-deprived rats consuming a 30-min test meal of sweetened mash. The anorectic effect of CCK-8 (4.0 nmol/kg, IP) was antagonized in a dose-dependent manner by DVZ (0.03, 0.10, and 0.30 #mol/kg, IP), with even the lowest dose producing a significant reversal. Under identical testing conditions, a supramaximal dose of DVZ (.75/~mol/kg) did not attenuate the reductions in food intake produced by either a moderate (4.0 pmol/kg) or a high dose (10.0/~mol/kg) of 5-HT. These data confirm established findings that the anorectic action of peripheral CCK depends upon CCK-A receptors. However, peripherally administered 5-HT reduces food intake independently of CCKergic function.

Research paper thumbnail of Peripheral serotonin is an incomplete signal for eliciting satiety in sham-feeding rats

Pharmacology Biochemistry and Behavior, 1992

WANG. Peripheral serotonin is an incomplete signal for eliciting satiety in sham-feeding rats. PH... more WANG. Peripheral serotonin is an incomplete signal for eliciting satiety in sham-feeding rats. PHARMACOL BIOCHEM BEHAV 43(3) 847-854, 1992. -Peripheral administration of serotonin [5-hydroxytryptamine (5-HT)] to rats equipped with gastric cannulae reduced their 30-rain consumption of sweetened milk after overnight deprivation whether the cannniae were closed (real feeding) or open (sham feeding). The anorectic action of 5-HT (1.6, 4.0, and 10.0 #mol/kg, IP) in sham feeding was dose-related, rapid in onset, and persisted during the 30-rain testing session. However, 5-HT failed to elicit resting--the terminal behavioral phase of satiety-in sham-feeding rats. Direct comparison of the effects of 4.0 #mol/kg 5-HT under both feeding conditions established that this dose promoted resting only when rats fed with their cannulae closed. The actions of 5-HT on feeding and resting were behaviorally selective because serotonergic treatment did not retard the beginning of feeding, alter sham drinking of water, or reduce investigation by food-deprived rats of a novel object in an open field. Together, the results suggest that 5-HT exerts separate actions to inhibit feeding and accelerate the process of satiation as marked by resting. However, peripheral 5-HT is inadequate as a signal for modulating satiety in the absence of postingestive stimuli.

Research paper thumbnail of Increased m-CPP-induced oral dyskinesia after lesion of serotonergic neurons

Pharmacology Biochemistry and Behavior, 2001

Peripheral administration of the 5-hydroxytryptamine (5-HT)(2C/1B) agonist 1-(m-chlorophenyl)pipe... more Peripheral administration of the 5-hydroxytryptamine (5-HT)(2C/1B) agonist 1-(m-chlorophenyl)piperazine (m-CPP) produces abnormal orofacial movements in rats. We have previously shown that this behavior is mediated by 5-HT(2C) receptors in the subthalamic nucleus [Neuroscience 72 (1996) 117]. The present studies examined this effect after serotonin depletion to determine whether removal of endogenous serotonin affected this behavioral response and/or subthalamic 5-HT(2C) receptors. Rats received an intraventricular infusion of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT, 100 mg/10 ml) or vehicle after desipramine pretreatment (25 mg/kg ip). The efficacy of serotonin depletion was confirmed by a decrease in serotonin uptake sites measured by autoradiography. Oral dyskinesia induced by peripheral administration of m-CPP (1.0 mg/kg ip) was markedly increased in lesioned rats compared to sham-operated controls 4 and 8 but not 12 days after the lesion. A subset of lesioned rats that displayed transient seizures after m-CPP injection did not prevent the measurement of oral dyskinesia during the observation period. No differences in 5-HT(2C) receptor levels were found with ligand-binding autoradiography in the subthalamic nucleus, or in other brain regions that express this receptor, in rats sacrificed 5 days following 5,7-DHT lesions. The data indicate that lesion of serotonergic neurons in adult rats induces a transient increase in motor responses mediated by subthalamic 5-HT(2C) receptors. These data suggest that functional alterations in serotonergic transmission in the subthalamic nucleus may be involved in the pathophysiology of hyperkinetic movement disorders.

Research paper thumbnail of A role for the subthalamic nucleus in 5-HT2C-induced oral dyskinesia

Neuroscience, 1996

The 5-hydroxytryptamine2c serotonin receptor is broadly distributed in brain, however its functio... more The 5-hydroxytryptamine2c serotonin receptor is broadly distributed in brain, however its functional role is unknown. Peripheral administration of drugs acting at the 5-hydroxytryptamine2c receptor induces abnormal oral dyskinesias, hyperkinetic motor disorders that often result from dysfunction of the basal ganglia. The subthalamic nucleus, a brain region anatomically and functionally related to the basal ganglia, has been implicated in oral dyskinesia. The subthalamic nucleus contains messenger RNA encoding 5-hydroxytryptamine~c receptors, suggesting its potential role in 5-hydroxytryptaminezc-mediated oral dyskinesia. Both systemic administration and local unilateral infusion of the 5-hydroxytryptamine2c/l B agonist, 1-(m-chlorophenyl)piperazine into the subthalamic nucleus increased orofacial movements. Oral movements following subthalamic infusion of 1-(m-chlorophenyl)piperazine were blocked by systemic administration of the 5-hydroxytryptamine2c/2 A antagonists mianserin, ketanserin and mesulergine but were not altered by systemic pretreatment with either the 5-hydroxytrypt-amine~A/2 A and dopamine antagonist spiperone or the 5-hydroxytryptaminelA/l B antagonist pindolol. Co-infusion of mesulergine with l-(m-chlorophenyl)piperazine into the subthalamic nucleus blocked 1-(m-chlorophenyl)piperazine-stimulated oral movements. Oral bouts following systemically administered 1-(m-chlorophenyl)piperazine were markedly reduced following bilateral subthalamic infusion of either mesulergine or the selective 5-hydroxytryptamine2c antagonist SDZ SER 082. The findings indicate that stimulating 5-hydroxytryptamine2c receptors in the subthalamic nucleus elicits orofacial dyskinesia in the rat.

Research paper thumbnail of Pattern of expression of the serotonin2C receptor messenger RNA in the basal ganglia of adult rats

The Journal of Comparative Neurology, 1997

The distribution of the serotonin (5-HT) receptor 5-HT2C mRNA was examined at the single-cell lev... more The distribution of the serotonin (5-HT) receptor 5-HT2C mRNA was examined at the single-cell level with in situ hybridization histochemistry and emulsion autoradiography in the basal ganglia and mesolimbic system of adult rats, with focus on the pallidum and the substantia nigra, which receive striatal inputs and play a critical role in basal ganglia function. 5-HT2C receptor mRNA expression was always restricted to a subpopulation of neurons in the regions examined. In the neostriatum, labeled neurons were more numerous in the rostral nucleus accumbens than in the caudal nucleus accumbens and were more numerous in the ventral and ventrolateral caudate-putamen than in the dorsal caudate-putamen, where labeled neurons were restricted to isolated clusters. In striatal target areas, dense labeling in the entopeduncular nucleus (internal pallidum, direct striatal output pathway) contrasted with an absence of labeling in the globus pallidus (external pallidum, indirect striatal output pathway). Double-label in situ hybridization in the substantia nigra revealed coexpression of 5-HT2C receptor mRNA with glutamic acid decarboxylase but not with tyrosine hydroxylase mRNA, indicating that it was restricted to gamma-aminobutyric acid (GABA)ergic neurons. In this region, dense labeling for 5-HT2C mRNA was found in half of the neurons at middle and caudal levels of both the pars compacta and the pars reticulata, with little labeling rostrally. The data suggest that drugs acting on the 5-HT2C receptor could selectively affect discrete neuronal populations in the basal ganglia and mesolimbic systems and indicate a new level of neurochemical heterogeneity among GABAergic neurons of the substantia nigra.

Research paper thumbnail of Dopaminergic Stimulation of Subthalamic Nucleus Elicits Oral Dyskinesia in Rats

Experimental Neurology, 1994

Research paper thumbnail of Peripherally administered ??-methyl-5-hydroxy-tryptamine and 5-carboxamidotryptamine reduce food intake via different mechanisms in rats

Behavioural Pharmacology, 1990

Research paper thumbnail of Serotonergic mechanisms and ingestion: Pharmacological facts and physiological promises

Research paper thumbnail of Serotonin (5-HT) and Cholecystokinin (CCK) contract the isolated rat pylorus by distinct pharmacological mechanisms

Research paper thumbnail of Serotonin-induced muscle contraction in rat stomach fundus is mediated by a G alpha z-like guanine nucleotide binding protein

The Journal of pharmacology and experimental therapeutics, 1993

Serotonin (5-HT) potently contracts the fundus of the rat stomach; however, the associated transd... more Serotonin (5-HT) potently contracts the fundus of the rat stomach; however, the associated transduction pathway has not been described fully. Experiments were performed in an attempt to gain insight into the coupling mechanism associated with this fundal 5-HT receptor. 5-HT-stimulated [35S]GTP gamma S binding to a protein which was recognized by anti-G alpha Z antiserum in a Mg(++)-dependent fashion. 5-HT increased [35S]GTP gamma S binding in the fundus, but not in the corpus of the rat stomach. 5-HT also enhanced the binding of [alpha-32P]GTP to the fundal protein and increased the hydrolysis of GTP to GDP in fundal membranes. The fundal protein which binds GTP is 25 to 29 kDa in size whereas the brain G alpha Z protein which is recognized by the anti-G alpha Z antibody is a 41 kDa protein. Mixing experiments revealed that the fundal guanine nucleotide binding protein does not appear to be a proteolytic product of the 41 kDa G alpha Z protein. Activating protein kinase C with phorb...

Research paper thumbnail of Peripherally administered alpha-methyl-5-hydroxy-tryptamine and 5-carboxamidotryptamine reduce food intake via different mechanisms in rats

Behavioural pharmacology, 1989

Peripherally administering the serotonin (5-HT) analogs, alpha-methyl-5-hydroxytryptamine (alpha-... more Peripherally administering the serotonin (5-HT) analogs, alpha-methyl-5-hydroxytryptamine (alpha-Me-5-HT) and 5-carboxamidotryptamine (5-CT), reduced milk consumption by food-deprived rats. 5-CT decreased milk intake 100-fold more potently than alpha-Me-5-HT (ID(50)'s =.06 and 5.6µmol/kg, respectively). 5-CT also elicited drinking but alpha-Me-5-HT did not. The nonselective 5-HT antagonist, methysergide, blocked the anorectic actions of each agonist. By contrast, the 5-HT(2) antagonist, ketanserin, and the peripheral 5-HT(2) antagonist, xylamidine, only prevented anorexia due to alpha-Me-5-HT. These results suggest that stimulating either peripheral 5-HT(2) or peripheral 5-HT(1)-like receptors inhibits feeding in rats. 5-HT(1)-like sites may also mediate 5-HT-induced drinking.

Research paper thumbnail of Serotonin contracts the isolated rat pylorus via a 5-HT2-like receptor

The American journal of physiology, 1994

Serotonin (5-HT) produced concentration-dependent contractions of the isolated rat pylorus in vit... more Serotonin (5-HT) produced concentration-dependent contractions of the isolated rat pylorus in vitro. Serotonergic contractions were antagonized by the calcium L-channel blocker, diltiazem, but not by tetrodotoxin or atropine. Three drugs that block 5-HT2 receptors, ketanserin, xylamidine, and methysergide, unsurmountably inhibited contractions to 5-HT. In contrast, antagonists of 5-HT3, 5-HT1A/1B, beta-adrenergic, or alpha 1-adrenergic receptors did not alter the response to 5-HT. Devazepide, an antagonist of cholecystokinin (CCK) type-A receptors, blocked contraction produced by CCK-8 but not by 5-HT. Conversely, the 5-HT2 antagonists did not affect CCK-stimulated contraction. These results suggest that 5-HT contracts the pylorus by a 5-HT2-like receptor on muscle and that this response occurs independently of CCKergic receptor mechanisms. Furthermore, the parallel between the overall pharmacological profile for serotonergic contraction of the pylorus and that observed previously f...

Research paper thumbnail of Abdominal vagotomy dissociates the anorectic mechanisms for peripheral serotonin and cholecystokinin

The American journal of physiology, 1993

These studies compared the effects of total abdominal vagotomy (VGX) on ingestive actions produce... more These studies compared the effects of total abdominal vagotomy (VGX) on ingestive actions produced by peripheral serotonergic and cholecystokinergic (CCKergic) stimulation in rats. Subcutaneous injection of 0.01-0.16 mumol/kg of the serotonin (5-HT) analogue 5-carboxamidotryptamine (5-CT) dose-dependently reduced mash intake equally in VGX rats and their laparotomized (LAP) controls but concurrently stimulated drinking only in the controls. The sulfated octapeptide of cholecystokinin (CCK-8, 4.0 nmol/kg ip) also reduced food intake only in the controls. In a second set of rats, vagotomy did not alter anorexia after intraperitoneal administration of either 2.0 or 8.0 mumol/kg of 5-HT or of 0.03 mumol/kg of 5-CT but abolished anorexia after a large dose of CCK-8 (8.0 nmol/kg). The completeness of vagotomy was verified histologically by immunohistochemical staining of the vagal bundles for the high molecular weight form of neurofilament-H protein. We report for the first time that 5-CT...

Research paper thumbnail of The CCK-A receptor antagonist, devazepide, blocks the anorectic action of CCK but not peripheral serotonin in rats

Pharmacology Biochemistry and Behavior, 1992

The CCK-A receptor antagonist, devazepide, blocks the anorectic action of CCK but not peripheral ... more The CCK-A receptor antagonist, devazepide, blocks the anorectic action of CCK but not peripheral serotonin in rats. PHARMACOL BIOCHEM BEHAV 43(3), 943-947, 1992.-A role has been proposed for cholecystokinin (CCK)-A-type receptors in mediating the anorectic action produced by serotonergic stimulation in rats. We examined the effect of pretreatment with the CCK-A antagonist devazepide (DVZ) on anorexia produced by peripheral administration of serotonin [5-hydroxytryptamine (5-HT)] or CCK-8 in 3-h food-deprived rats consuming a 30-min test meal of sweetened mash. The anorectic effect of CCK-8 (4.0 nmol/kg, IP) was antagonized in a dose-dependent manner by DVZ (0.03, 0.10, and 0.30 #mol/kg, IP), with even the lowest dose producing a significant reversal. Under identical testing conditions, a supramaximal dose of DVZ (.75/~mol/kg) did not attenuate the reductions in food intake produced by either a moderate (4.0 pmol/kg) or a high dose (10.0/~mol/kg) of 5-HT. These data confirm established findings that the anorectic action of peripheral CCK depends upon CCK-A receptors. However, peripherally administered 5-HT reduces food intake independently of CCKergic function.

Research paper thumbnail of Peripheral serotonin is an incomplete signal for eliciting satiety in sham-feeding rats

Pharmacology Biochemistry and Behavior, 1992

WANG. Peripheral serotonin is an incomplete signal for eliciting satiety in sham-feeding rats. PH... more WANG. Peripheral serotonin is an incomplete signal for eliciting satiety in sham-feeding rats. PHARMACOL BIOCHEM BEHAV 43(3) 847-854, 1992. -Peripheral administration of serotonin [5-hydroxytryptamine (5-HT)] to rats equipped with gastric cannulae reduced their 30-rain consumption of sweetened milk after overnight deprivation whether the cannniae were closed (real feeding) or open (sham feeding). The anorectic action of 5-HT (1.6, 4.0, and 10.0 #mol/kg, IP) in sham feeding was dose-related, rapid in onset, and persisted during the 30-rain testing session. However, 5-HT failed to elicit resting--the terminal behavioral phase of satiety-in sham-feeding rats. Direct comparison of the effects of 4.0 #mol/kg 5-HT under both feeding conditions established that this dose promoted resting only when rats fed with their cannulae closed. The actions of 5-HT on feeding and resting were behaviorally selective because serotonergic treatment did not retard the beginning of feeding, alter sham drinking of water, or reduce investigation by food-deprived rats of a novel object in an open field. Together, the results suggest that 5-HT exerts separate actions to inhibit feeding and accelerate the process of satiation as marked by resting. However, peripheral 5-HT is inadequate as a signal for modulating satiety in the absence of postingestive stimuli.

Research paper thumbnail of Increased m-CPP-induced oral dyskinesia after lesion of serotonergic neurons

Pharmacology Biochemistry and Behavior, 2001

Peripheral administration of the 5-hydroxytryptamine (5-HT)(2C/1B) agonist 1-(m-chlorophenyl)pipe... more Peripheral administration of the 5-hydroxytryptamine (5-HT)(2C/1B) agonist 1-(m-chlorophenyl)piperazine (m-CPP) produces abnormal orofacial movements in rats. We have previously shown that this behavior is mediated by 5-HT(2C) receptors in the subthalamic nucleus [Neuroscience 72 (1996) 117]. The present studies examined this effect after serotonin depletion to determine whether removal of endogenous serotonin affected this behavioral response and/or subthalamic 5-HT(2C) receptors. Rats received an intraventricular infusion of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT, 100 mg/10 ml) or vehicle after desipramine pretreatment (25 mg/kg ip). The efficacy of serotonin depletion was confirmed by a decrease in serotonin uptake sites measured by autoradiography. Oral dyskinesia induced by peripheral administration of m-CPP (1.0 mg/kg ip) was markedly increased in lesioned rats compared to sham-operated controls 4 and 8 but not 12 days after the lesion. A subset of lesioned rats that displayed transient seizures after m-CPP injection did not prevent the measurement of oral dyskinesia during the observation period. No differences in 5-HT(2C) receptor levels were found with ligand-binding autoradiography in the subthalamic nucleus, or in other brain regions that express this receptor, in rats sacrificed 5 days following 5,7-DHT lesions. The data indicate that lesion of serotonergic neurons in adult rats induces a transient increase in motor responses mediated by subthalamic 5-HT(2C) receptors. These data suggest that functional alterations in serotonergic transmission in the subthalamic nucleus may be involved in the pathophysiology of hyperkinetic movement disorders.

Research paper thumbnail of A role for the subthalamic nucleus in 5-HT2C-induced oral dyskinesia

Neuroscience, 1996

The 5-hydroxytryptamine2c serotonin receptor is broadly distributed in brain, however its functio... more The 5-hydroxytryptamine2c serotonin receptor is broadly distributed in brain, however its functional role is unknown. Peripheral administration of drugs acting at the 5-hydroxytryptamine2c receptor induces abnormal oral dyskinesias, hyperkinetic motor disorders that often result from dysfunction of the basal ganglia. The subthalamic nucleus, a brain region anatomically and functionally related to the basal ganglia, has been implicated in oral dyskinesia. The subthalamic nucleus contains messenger RNA encoding 5-hydroxytryptamine~c receptors, suggesting its potential role in 5-hydroxytryptaminezc-mediated oral dyskinesia. Both systemic administration and local unilateral infusion of the 5-hydroxytryptamine2c/l B agonist, 1-(m-chlorophenyl)piperazine into the subthalamic nucleus increased orofacial movements. Oral movements following subthalamic infusion of 1-(m-chlorophenyl)piperazine were blocked by systemic administration of the 5-hydroxytryptamine2c/2 A antagonists mianserin, ketanserin and mesulergine but were not altered by systemic pretreatment with either the 5-hydroxytrypt-amine~A/2 A and dopamine antagonist spiperone or the 5-hydroxytryptaminelA/l B antagonist pindolol. Co-infusion of mesulergine with l-(m-chlorophenyl)piperazine into the subthalamic nucleus blocked 1-(m-chlorophenyl)piperazine-stimulated oral movements. Oral bouts following systemically administered 1-(m-chlorophenyl)piperazine were markedly reduced following bilateral subthalamic infusion of either mesulergine or the selective 5-hydroxytryptamine2c antagonist SDZ SER 082. The findings indicate that stimulating 5-hydroxytryptamine2c receptors in the subthalamic nucleus elicits orofacial dyskinesia in the rat.

Research paper thumbnail of Pattern of expression of the serotonin2C receptor messenger RNA in the basal ganglia of adult rats

The Journal of Comparative Neurology, 1997

The distribution of the serotonin (5-HT) receptor 5-HT2C mRNA was examined at the single-cell lev... more The distribution of the serotonin (5-HT) receptor 5-HT2C mRNA was examined at the single-cell level with in situ hybridization histochemistry and emulsion autoradiography in the basal ganglia and mesolimbic system of adult rats, with focus on the pallidum and the substantia nigra, which receive striatal inputs and play a critical role in basal ganglia function. 5-HT2C receptor mRNA expression was always restricted to a subpopulation of neurons in the regions examined. In the neostriatum, labeled neurons were more numerous in the rostral nucleus accumbens than in the caudal nucleus accumbens and were more numerous in the ventral and ventrolateral caudate-putamen than in the dorsal caudate-putamen, where labeled neurons were restricted to isolated clusters. In striatal target areas, dense labeling in the entopeduncular nucleus (internal pallidum, direct striatal output pathway) contrasted with an absence of labeling in the globus pallidus (external pallidum, indirect striatal output pathway). Double-label in situ hybridization in the substantia nigra revealed coexpression of 5-HT2C receptor mRNA with glutamic acid decarboxylase but not with tyrosine hydroxylase mRNA, indicating that it was restricted to gamma-aminobutyric acid (GABA)ergic neurons. In this region, dense labeling for 5-HT2C mRNA was found in half of the neurons at middle and caudal levels of both the pars compacta and the pars reticulata, with little labeling rostrally. The data suggest that drugs acting on the 5-HT2C receptor could selectively affect discrete neuronal populations in the basal ganglia and mesolimbic systems and indicate a new level of neurochemical heterogeneity among GABAergic neurons of the substantia nigra.

Research paper thumbnail of Dopaminergic Stimulation of Subthalamic Nucleus Elicits Oral Dyskinesia in Rats

Experimental Neurology, 1994

Research paper thumbnail of Peripherally administered ??-methyl-5-hydroxy-tryptamine and 5-carboxamidotryptamine reduce food intake via different mechanisms in rats

Behavioural Pharmacology, 1990

Research paper thumbnail of Serotonergic mechanisms and ingestion: Pharmacological facts and physiological promises

Research paper thumbnail of Serotonin (5-HT) and Cholecystokinin (CCK) contract the isolated rat pylorus by distinct pharmacological mechanisms

Research paper thumbnail of Serotonin-induced muscle contraction in rat stomach fundus is mediated by a G alpha z-like guanine nucleotide binding protein

The Journal of pharmacology and experimental therapeutics, 1993

Serotonin (5-HT) potently contracts the fundus of the rat stomach; however, the associated transd... more Serotonin (5-HT) potently contracts the fundus of the rat stomach; however, the associated transduction pathway has not been described fully. Experiments were performed in an attempt to gain insight into the coupling mechanism associated with this fundal 5-HT receptor. 5-HT-stimulated [35S]GTP gamma S binding to a protein which was recognized by anti-G alpha Z antiserum in a Mg(++)-dependent fashion. 5-HT increased [35S]GTP gamma S binding in the fundus, but not in the corpus of the rat stomach. 5-HT also enhanced the binding of [alpha-32P]GTP to the fundal protein and increased the hydrolysis of GTP to GDP in fundal membranes. The fundal protein which binds GTP is 25 to 29 kDa in size whereas the brain G alpha Z protein which is recognized by the anti-G alpha Z antibody is a 41 kDa protein. Mixing experiments revealed that the fundal guanine nucleotide binding protein does not appear to be a proteolytic product of the 41 kDa G alpha Z protein. Activating protein kinase C with phorb...