Differential effect of neuroleptic drugs on dopamine turnover in the extrapyramidal and limbic system

Bartholini, G.

doi:10.1111/j.2042-7158.1976.tb04648.x

Cited by 176 publications

(35 citation statements)

References 17 publications

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“…The anti-dopamine character of sulpiride in the central nervous system has been described in many reports (1,(17)(18)(19)(20)(21)(22)(23). However, the drug was reported not to block the dopamine-sensitive adenylate cyclase (24,25).…”

Section: Discussionmentioning

confidence: 99%

Dopamine Receptor Blocking Activity of Sulpiride in the Canine Exocrine Pancreas

Satoh

Honda

1980

Japanese Journal of Pharmacology

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Abstract-The inhibitory effect of sulpiride on dopamine receptors was investigated in the exocrine pancreas of dogs anesthetized with pentobarbital and with the stomach ligated at the pylorus. All test substances were given intravenously. Dopamine, acetylcholine, histamine and secretin produced a dose-related increase in pancreatic juice secretion, though the dose-effect curves of these secretagogues differed in shape. Epinephrine, norepinephrine, isoproterenol, methamphetamine and serotonin had no secretagogue effects. The effects of acetylcholine and histamine were inhibited by atropine and cimetidine, respectively. The effect of dopamine was blocked by halo peridol, but not by atropine, cimetidine, phentolamine and propranolol. These results suggest that dopamine acts on specific dopamine receptors related to the exocrine pancreatic secretion.Haloperidol had no effect on the effects of acetylcholine and histamine, but did inhibit the secretin-induced secretion, though the inhibitory effect was to a lesser extent than on the dopamine response. Sulpiride and chlorpromazine also suppressed dose-dependently the dopamine-induced secretion. The inhibitory activity of sulpiride was almost the same as that of haloperidol, and 12 times more potent than that of chlorpromazine.Sulpiride was found to be a potent dopamine antagonist in the canine exocrine pancreas.In a previous report we showed that sulpiride`, an antipsychotic drug, has essentially a potent inhibition on dopamine receptors in the central nervous system. This drug, when given intraventricularly to rats, was equally or more effective than haloperidol in inducing catalepsy and in inhibiting apomorphine and methamphetamine-induced circling behavior (1). The present paper deals with antagonism of sulpiride to dopamine in the exocrine pancreas of dogs.Hashimoto and collaborators demonstrated that exogenous dopamine increases the secretion of pancreatic juice, of which the components are similar to those induced by exogenous secretin (2), and that there are specific dopamine receptors related to the exocrine pancreatic secretion in dogs (3-6). Thus, the dopamine receptor response can be easily quantified by measuring the increases in volume of the pancreatic juice. This system is a convenient tool for studies on the interaction between dopamine and test substances.We attempted to evaluate the antidoparnine activity of sulpiride, chlorpromazine and haloperidol given to anesthetized dogs before an i.v. administration of dopamine in order to evoke increased pancreatic secretion. We also examined the specificity of the pancreatic dopamine receptor response to dopamine injected systemically, as the dopamine receptor

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Section: Discussionmentioning

confidence: 99%

Dopamine Receptor Blocking Activity of Sulpiride in the Canine Exocrine Pancreas

Satoh

Honda

1980

Japanese Journal of Pharmacology

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“…Previous studies also point to an interaction with some ionotropic receptors, for example, the N-methyl-D-aspartate (NMDA) receptor (Arvanov et al, 1997;Ossowska et al, 1999) and the GABA A receptor (Squires and Saederup, 1998). It has been suggested that clozapine has a preferential action on the mesolimbic DA system as compared to the nigrostriatal DA system (Andén and Stock, 1973;Bartholini, 1976;Bunney, 1983, 1985;Moghaddam and Bunney, 1990). Moreover, since clozapine is a potent serotonin 5-HT 2 -receptor antagonist, it has been suggested that concurrent 5-HT 2 and DA-D 2 receptor antagonism may contribute to its atypical profile (see Deutch et al, 1991;Ichikawa et al, 2001;Meltzer and Nash, 1991).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Action of Clozapine on Rat Ventral Tegmental Area Dopamine Neurons Following Increased Levels of Endogenous Kynurenic Acid

Schwieler

Erhardt

2003

Neuropsychopharmacol

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The mode of action by which the atypical antipsychotic drug clozapine exerts its superior efficacy to ameliorate both positive and negative symptoms is still unknown. In the present in vivo electrophysiological study, we investigate the effects of haloperidol (a typical antipsychotic drug) and clozapine on ventral tegmental area (VTA) dopamine (DA) neurons in a situation of hyperdopaminergic activity in order to mimic tentatively a condition similar to that seen in schizophrenia. Increased DA transmission was induced by elevating endogenous levels of the N-methyl-D-aspartate receptor and a7* nicotinic receptor antagonist kynurenic acid (KYNA; by means of PNU 156561A, 40 mg /kg, i.v.). In control rats, i.v. administered haloperidol (0.05-0.8 mg/kg) or clozapine (1.25-10 mg/kg) was associated with increased firing rate and burst firing activity of VTA DA neurons. However, in rats displaying hyperdopaminergia (induced by elevated levels of KYNA), the effects of clozapine on VTA DA neurons were converted into pure inhibitory responses, including decrease in burst firing activity. In contrast, haloperidol still produced an excitatory action on VTA DA neurons in rats with elevated levels of endogenous brain KYNA. The results of the present study suggest that clozapine facilitates or inhibits VTA DA neurotransmission, depending on brain concentration of KYNA. Such an effect of clozapine may be related to its unique effect in also ameliorating negative symptoms of schizophrenia.

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“…There may also be a variety of regional differences in the microenvironment surrounding the receptor-enzyme complex, such as the presence or absence within the membranes of certain neuroregulators that interact with the adenylate cyclase system. Dopamine turnover in the mesolimbic terminal region has been shown to differ from striatum in response to short-or long-term treatment with neuroleptics (e.g., Bartholini, 1976;Kaneno et al, 1978;Scatton et al, 1977). Moreover, basal rates of dopamine synthesis and metabolism are quite different in these 2 brain regions.…”

Section: Discussionmentioning

confidence: 99%

Differential down-regulation of D1-stimulated adenylate cyclase activity in rat forebrain after in vivo amphetamine treatments

Roberts-Lewis¹,

Ph²,

Iwaniec³

et al. 1986

J. Neurosci.

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Amphetamine has complex behavioral actions in the rat that depend upon the release of dopamine in striatal and mesolimbic brain regions. To explore a possible role of the dopamine-sensitive CAMP second-messenger system in mediating these effects, we examined the effects of in viva amphetamine treatments on the Dl receptor-coupled adenylate cyclase system in membranes from striatal and mesolimbic rat brain regions. The results show that amphetamine produces a regional, dose-and time-dependent down-regulation of adenylate cyclase activity. Intermediate and high doses of amphetamine (2.5 and 7.5 mg/kg, respectively), but not a low dose (1.0 mg/kg), resulted in a decrease in the apparent Vmx and/or an increase in the apparent K. for the selective Dl partial agonist, SKF38393, in striatal membranes 30 min after amphetamine treatment. Treatment of rats with 7.5 mg/kg amphetamine for 30 and 60 min, but not 10 min, similarly resulted in a down-regulation of Dl-mediated adenylate cyclase activity in striatal membranes. In contrast, in mesolimbit tissues, no amphetamine treatment at any time resulted in an alteration of SKF38393-stimulated adenylate cyclase activity relative to saline controls. The results of behavioral analyses also showed that animals exhibiting intense stereotypies had significantly lower striatal apparent V,, values than did those animals engaged in moderate or no behavioral activity at the time of decapitation. These findings demonstrate that amphetamine treatments result in a down-regulation of striatal, but not mesolimbic, dopamine-sensitive adenylate cyclase activity that parallels the intense, stereotyped behaviors characteristic of dopaminergic activation in the striatum.Amphetamine (AMPH), a phenylethylamine derivative, is a potent CNS stimulant with a multiplicity of behavioral and physiological effects (see Tepper, 1983, andSchuckit, 1983, for reviews). At lower doses of AMPH (1 .O mg/kg), rats exhibit enhanced locomotor activity and exploratory behaviors. As the dose is increased (e.g., 2.5 mg/kg), rats begin to show episodic bouts of repetitive head and limb movements (stereotypies). After a high dose of AMPH (5-7.5 mg/ kg), a similar sequence of behaviors may be observed as a function of time after AMPH administration. Shortly after the drug injection (ca. 10 min), rats show a marked increase in rearing and sniffing, or locomotor activity, followed (ca. 30 min) by stereotyped head and limb movements. By 60 min after AMPH administration, most animals are engaged in intense, continuous stereotypy, head oriented down toward the cage floor, often accompanied by oral stereotypies such as licking or gnawing. These multiphasic time-and dose-dependent behavioral effects

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Differential effect of neuroleptic drugs on dopamine turnover in the extrapyramidal and limbic system

Cited by 176 publications

References 17 publications

Dopamine Receptor Blocking Activity of Sulpiride in the Canine Exocrine Pancreas

Dopamine Receptor Blocking Activity of Sulpiride in the Canine Exocrine Pancreas

Inhibitory Action of Clozapine on Rat Ventral Tegmental Area Dopamine Neurons Following Increased Levels of Endogenous Kynurenic Acid

Differential down-regulation of D1-stimulated adenylate cyclase activity in rat forebrain after in vivo amphetamine treatments

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