The influence of 5-hydroxytryptamine on the release of acetylcholine from guinea-pig brain ex vivo and in vitro.
The effect of 5-hydroxytryptamine (5-HT) on the release of acetylcholine (ACh) from the brain of the guinea-pig was investigated in order to determine whether this amine plays a modulatory role on the cortical cholinergic projections. 5-Hydroxytryptamine (0.2-1 mumol), injected intracerebroventricularly (i.c.v.), caused mild excitation, stereotyped movements and ataxia. Simultaneously, it increased the output of ACh from the cortex in a dose-dependent manner. Methysergide (4.2 mumol Kg-1 i.p.) also increased the output of ACh by about 60-80%, but prevented the effect of 5-HT (1 mumol i.c.v.). Metitepine (1-4.2 mumol kg-1 i.p.) increased the output of ACh like methysergide but it changed the facilitation of the release of ACh by 5-HT into inhibition. At the same time the animals became hypothermic, sedated and their electroencephalogram (EEG) was synchronized. Pretreatment with 5,7-HT blocked the increase in release of ACh produced by 5-HT (1 mumol). D-Norfenfluramine (10.4 mumol kg-1) was ineffective alone but reduced the release of ACh in metitepine-pretreated animals. 5-Hydroxytryptamine (10-30 microM) did not affect the efflux of [3H]choline from electrically-stimulated slices of cerebral cortex. The increase in the release of ACh caused by 5-HT, abolished by pretreatment with methysergide and 5,7-HT, may be explained by activation of 5-HT autoreceptors, while the increase of transmitter outflow induced by methysergide may be due to a blockade of 5-HT receptors present on the cholinergic neurones. Metitepine appeared to unmask the tryptaminergic inhibition caused by injection of 5-HT intraventricularly or by the 5-HT-releasing drug, D-norfenfluramine, possibly by acting on the autoreceptors and preventing auto-inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004569:Electroencephalography; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D006168:Guinea Pigs; D007276:Injections, Intraventricular; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009642:Norfenfluramine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*
D009642:Norfenfluramine; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D000109:Acetylcholine; D010134:Fenclonine; D008784:Methysergide