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5‐HT 1A agonists increase and 5‐HT 3 agonists decrease acetylcholine efflux from the cerebral cortex of freely‐moving guinea‐pigs
Author(s) -
Bianchi Clementina,
Siniscalchi Anna,
Beani Lorenzo
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12728.x
Subject(s) - acetylcholine , ketanserin , endocrinology , chemistry , medicine , cholinergic , 5 ht receptor , autoreceptor , stimulation , cerebral cortex , muscarinic acetylcholine receptor , serotonin , agonist , pharmacology , biology , receptor
1 The influence of 5‐hydroxytryptamine 1A (5‐HT 1A ), 5‐HT 2 and 5‐HT 3 agonists and antagonists on acetylcholine (ACh) release from the cerebral cortex was studied in freely moving guinea‐pigs. 2 8‐Hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT, 0.01–1 mg kg −1 , s.c.) caused the 5‐HT syndrome and dose‐dependently increased ACh release. Ru 24969 (1–10 mg kg −1 , s.c.) shared the same effects, but it was less potent. (−)‐Propranolol (5 mg kg −1 ) and metitepine (2 mg kg −1 ) prevented these behavioural and neurochemical responses. 3 (±)‐1(4‐Iodo‐2,5‐dimethoxyphenyl)2‐aminopropane (DOI) up to 2 mg kg −1 did not modify ACh release and ketanserin (0.5 mg kg −1 ) was ineffective on 5‐HT‐induced changes of ACh outflow. 4 2‐Methyl‐5‐HT (500 μg, i.c.v.) and 5‐HT (500 μg, i.c.v.) plus metitepine (2 mg kg −1 , s.c.) inhibited the gross behaviour and ACh release. ICS 205–930 (0.5 mg kg −1 ) prevented these responses. 5 2‐Methyl‐5‐HT, up to 10 μmoll −1 , and 8‐OH‐DPAT, up to 0.1 μmoll −1 , (like 5‐HT) did not change [ 3 H]‐choline efflux from cerebral cortex slices. 6 These results suggest that exogenous 5‐HT and related selective agonists modulate guinea‐pig cortical cholinergic structures through 5‐HT 1A and 5‐HT 3 receptors. The stimulation of 5‐HT 1A autoreceptors may lead to disinhibition of the cholinergic cells, tonically inhibited by the tryptaminergic control. Conversely, the stimulation of 5‐HT 3 receptors inhibits ACh release, possibly through an interneurone. No direct 5‐HT modulation of the cholinergic nerve endings was found.