Naunyn-Schmiedeberg's archives of pharmacology
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Naunyn Schmiedebergs Arch. Pharmacol. · Dec 1995
Differential modulation by muscimol and baclofen on antinociception induced by morphine, beta-endorphin, D-Pen2,5-enkephalin and U50,488H administered intracerebroventricularly in the mouse.
The present study was designed to investigate the modulatory effects of stimulation of GABAA and GABAB receptors at supraspinal sites on antinociception induced by supraspinally administered mu-, epsilon-, delta-, and kappa-opioid receptor agonists. The effects of the GABAA and GABAB receptor agonists, muscimol and baclofen respectively, on the antinociception induced by morphine (a mu-receptor agonist), beta-endorphin (an epsilon-receptor agonist), D-Pen2,5-enkephalin (DPDPE, a delta-receptor agonist) and U50,488H ([trans-3,4-dichloroN-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeocetamide]; a kappa-receptor agonist) injected intracerebroventricularly (i.c.v.) were studied. The antinociception was assayed using the tail-flick and hot-plate tests. ⋯ Baclofen (1.25-10 ng) administered i.c.v. alone did not affect the latencies of the tail-flick and hot-plate responses, but attenuated dose-dependently the inhibition of the tail-flick and hot-plate responses induced by beta-endorphin and U50,488H, without affecting morphine- or DPDPE-induced responses. Our results indicate that activation of GABAA receptors at the supraspinal sites by i.c.v. injection of muscimol antagonizes antinociception induced by supraspinally administered mu-, epsilon-, delta-, and kappa-opioid receptor agonists. On the other hand, activation of GABAB receptors at supraspinal sites by i.c.v. baclofen antagonizes antinociception induced by i.c.v. administered epsilon- and kappa-opioid agonists, but not mu- or delta-opioid agonists.
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Naunyn Schmiedebergs Arch. Pharmacol. · Oct 1995
Ritanserin potentiates the stimulatory effects of raclopride on neuronal activity and dopamine release selectivity in the mesolimbic dopaminergic system.
The atypical profile of clozapine and some other new antipsychotic drugs has been attributed to a relatively selective effect on the mesolimbic dopaminergic system, as well as to their potent serotonin 5-HT2 receptor antagonism and high ratio of 5-HT2 to dopamine D2 receptor affinities. It is unclear, however, how concurrent 5-HT2 and D2 receptor antagonism specifically affects the mesoaccumbens and the mesocortical dopaminergic systems. The present study examined the effect of pretreatment with the 5-HT2 receptor antagonist, ritanserin, on changes in midbrain dopamine neuronal activity as well as in forebrain, extracellular concentrations of dopamine, induced by relatively low doses of the D2 receptor antagonist raclopride, utilizing in vivo extracellular single cell recording techniques and voltammetry in anesthetized rats, as well as microdialysis in freely moving rats. ⋯ The stimulatory effect of the combined ritanserin plus raclopride treatment on neuronal activity and DA release was more pronounced in the mesolimbic than the nigrostriatal dopaminergic system. The present data indicate that concurrent 5-HT2 and D2 receptor antagonism selectively affects the activity of the mesolimbic dopaminergic system. These findings provide an experimental basis for the notion that combined 5-HT2 and D2 receptor antagonism may underlie the limbic mode of action of at least some atypical antipsychotic drugs and consequently contribute to their unique therapeutic effects.
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Naunyn Schmiedebergs Arch. Pharmacol. · May 1993
Prevention and reversal of motor and sensory peripheral nerve conduction abnormalities in streptozotocin-diabetic rats by the prostacyclin analogue iloprost.
The effects of the prostacyclin analogue iloprost on nerve function were examined in streptozotocin-diabetic rats. Rats were treated either with iloprost from induction of diabetes over 2 months in a preventive experiment, or for 1 month following a 1 month untreated period of diabetes in a reversal experiment. One and 2 months untreated diabetic control, non-diabetic control, and iloprost-treated non-diabetic groups were also used. ⋯ Iloprost treatment significantly attenuated this for both preventive (47%, P < 0.001) and reversal (50%, P < 0.001) studies. There was no effect on hypoxic resistance for non-diabetic rats. In the preventive group there was a 28% increase in sciatic nerve endoneurial capillary density (P < 0.001), a lesser effect (16%, P < 0.05) in the reversal group, and no effect in non-diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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Naunyn Schmiedebergs Arch. Pharmacol. · May 1993
Role of dopamine receptors in the dual effect of naloxone on quinpirole-induced yawning in morphine pretreated rats.
The present study was undertaken to determine the state of sensitivity of dopamine D2/D3 receptors involved in the mediation of yawning behaviour at various times following acute morphine administration to rats. Morphine (3.0 mg/kg, s.c.) induced a biphasic effect on locomotor activity: an initial inhibitory phase lasting for about 30 min was after about an hour followed by a phase of locomotor activation lasting for about 60 min. Dopamine D2/D3 receptor agonist quinpirole (0.01-0.1 mg/kg, s.c.) induced yawning behaviour in rats. ⋯ D1 receptor antagonist SCH 23390 [R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3- benzazepin-7-ol hemimaleate] at 0.01 mg/kg did not affect quinpirole-induced yawning or its inhibition by morphine. However, in rats which received morphine 90 min prior to testing yawning, SCH 23390 enhanced quinpirole-induced yawning behaviour as compared with morphine- or saline-pretreated animals. The data obtained in the present study indicate that morphine pretreatment initially induces a lack of responsiveness of the D2/D3 receptors mediating yawning behaviour and subsequently increases their sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
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Naunyn Schmiedebergs Arch. Pharmacol. · Oct 1992
Changes in cholecystokinin receptor binding in rat brain after selective damage of locus coeruleus projections by DSP-4 treatment.
Brain cholecystokinin (CCK)- and noradrenergic activities are two neurochemical systems implicated in anxiety and deficits in novelty-related behaviour. In order to clarify a possible interaction between CCK- and noradrenergic neurotransmission in the brain, DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], a neurotoxin that selectively destroys noradrenaline-containing nerve terminals originating from the locus coeruleus, was administered to rats IP (10 and 50 mg/kg) seven days before decapitation. Noradrenaline uptake was very markedly reduced in the frontal cortex and hippocampus of the DSP-4 treated animals, whereas the decrease in the hypothalamus was smaller but still statistically significant. ⋯ The time-course of the development of changes in CCK-8 binding paralleled with some lag the development of changes in noradrenaline uptake. These findings demonstrate the denervation of noradrenergic input from the locus coeruleus induces certain alterations in the CCKergic neurotransmission. These alterations are similar to those seen in rats with deficits in response to novel stimuli, and may therefore mediate the neophobic responses observed in animals after lesions of noradrenergic innervation of the forebrain.