Serotonergic modulation of acetylcholine release from cortex of freely moving rats.
The modulation of acetylcholine (ACh) release by 5-HT3 receptor activation was studied using in vivo microdialysis. Spontaneous and K+-stimulated ACh release were measured in frontoparietal cortex and hippocampus of freely moving rats. Two consecutive exposures to high K+ produced ACh release of similar magnitude. In the cortex, serotonin (5-HT) failed to alter spontaneous ACh release, but caused a concentration-dependent decrease of K+-evoked ACh release. Phenylbiguanide (PBG) and m-chlorophenylbiguanide, two selective 5-HT3 agonists, mimicked the 5-HT responses, but 8-hydroxy-2-(di-n-propylamino)tetralin, a selective 5-HT1A agonist, was without effect. However, PBG failed to modify K+-evoked ACh release from the hippocampus. Systemic and local administration of a highly selective 5-HT3 antagonist, tropisetron ((3-alpha-tropanyl)1H-indole-carboxylic acid ester) blocked the effect of both 5-HT and PBG. The inhibition of ACh release by PBG was sensitive to tetrodotoxin. These observations provide direct evidence that, in rat cortex, 5-HT modulates in-vivo release of ACh through activation of 5-HT3 receptors.
Giovannini
M G
MG
Dipartimento di Farmacologia Preclinica e Clinica, Universitá di Firenze, 50134 Firenze, Italy.
Ceccarelli
I
I
Molinari
B
B
Cecchi
M
M
Goldfarb
J
J
Blandina
P
P
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D008297:Male; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D000077526:Tropisetron
D001645:Biguanides; D007211:Indoles; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013779:Tetrodotoxin; D000077526:Tropisetron; D000109:Acetylcholine; D011188:Potassium; C008846:phenyl biguanide