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The involvement of dopamine receptors in the beneficial effects of intracerebroventricular injection of substance P, neurokinin A and senktide on the scopolamine-induced impairment of spontaneous alternation performance was investigated in mice. Scopolamine (1 mg/kg) significantly impaired spontaneous alternation performance, while substance P (0.1 microg), neurokinin A (0.3 microg), senktide (0.003 microg) and S(-)-sulpiride (10 mg/kg), a dopamine D2 receptor antagonist, improved the scopolamine (1 mg/kg)-induced disturbance of spontaneous alternation performance. However, the dopamine D1 receptor antagonist SCH23390 (7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine maleate) did not influence the scopolamine-induced disturbance of spontaneous alternation performance. The dopamine D2 receptor agonist RU24213 (N-n-propyl-N-phenylethyl-p-(3-hydroxyphenyl)-ethylamine hydrochloride) (1 mg/kg) but not the dopamine D1 receptor agonist SKF38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1 H-3-benzazepine hydrochloride) (3 and 10 mg/kg) reversed the beneficial effects of substance P (0.1 microg) and neurokinin A (0.3 microg) on the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance. In contrast, neither SKF38393 (3 and 10 mg/kg) nor RU24213 (0.3 and 1 mg/kg) significantly affected the beneficial effects of senktide (0.003 microg) on the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance. Although RU24213 (1 mg/kg) and SCH23390 (0.03 mg/kg) markedly decreased total arm entries, SKF38393 (10 mg/kg), RU24213 (1 mg/kg), SCH23390 (0.03 mg/kg) or S(-)-sulpiride (10 mg/kg) had no significant effects on spontaneous alternation performance. These results suggest that stimulation of dopamine D2 but not D1 receptors reverses the ameliorative effects of substance P and neurokinin A, whereas neither dopamine D1 nor D2 receptors play an important role in the beneficial effects of senktide on the scopolamine-induced impairment of spontaneous alternation performance associated with spatial working memory.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9683012&dopt=Abstract
Naunyn Schmiedebergs Arch Pharmacol. 1998 Jun;357(6):640-7.
Stimulatory and inhibitory effects of ethanol on hippocampal acetylcholine release.
Henn C, Loffelholz K, Klein J.
Department of Pharmacology, University of Mainz, Germany.
Using the microdialysis technique and sensitive HPLC procedures for the determination of acetylcholine (ACh) and ethanol, we investigated the release of ACh in rat hippocampus after acute ethanol administration. Systemic administration of ethanol (0.8 and 2.4 g/kg i.p.) led to peak ethanol concentrations of 21 and 42 mM in the hippocampus, respectively. The high dose caused a long-lasting inhibition of basal ACh release by up to 33%. Local infusion of scopolamine (1 microM) enhanced hippocampal ACh release up to eightfold in the presence of neostigmine (10 microM), and this stimulated release was also inhibited after systemic ethanol administration (by up to 45%). The low dose of ethanol (0.8 g/kg) led to a delayed stimulation of hippocampal ACh release. A stimulatory effect on ACh release was also observed when ethanol (50-100 mM) was infused directly into the hippocampus or into the septal area, i.e. to the origin of the cholinergic septohippocampal pathway; thus, the stimulatory effect may be mediated by a direct effect on cholinergic fibres. We conclude that ethanol exerts dual modulatory effects on the activity of the septohippocampal cholinergic fibres, depending on the dose and the site of administration. It is suggested that the inhibition of hippocampal ACh release by intoxicating doses of ethanol may contribute to the well-known cognitive and amnesic effects of ethanol intake.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9686940&dopt=Abstract
Arzneimittelforschung. 1998 Jun;48(6):625-8.
Anxiolytic and memory improving effects of moclobemide.
Nowakowska E, Chodera A, Kus K, Rybakowski J.
Department of Pharmacology, University School of Medicine, Poznan, Poland.
The anxiolytic and memory enhancing effects of moclobemide (p-chloro-N-(2-morphinoethyl)benzamide, CAS 71320-77-9, Ro 11-1163), a reversible and selective monoamine A oxidase inhibitor, were investigated in rats. It was found that the drug had an anxiolytic activity lasting in chronic experiments over 2 weeks. The used dose of the drug did not change animal locomotion in activity cages. In memory experiments (food finding time in maze), moclobemide exerted a favorable effect only after a single administration. In rats with scopolamine-impaired memory, moclobemide attenuated the effects of scopolamine in single and chronic experiments.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9689417&dopt=Abstract
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