Modulation of Dopamine Release from Neuron-Enriched Tissue Cultures by Cholinergic Agents

Modulation of 3H]dopamine release by cholinergic agents (acetylcholine, atropine, d-tubocurarine, oxotremorine, and nicotine) was studied in primary cell cultures derived from whole brains of foetal rats (17 days of gestation). Monolayer and aggregated neuron-enriched cultures were maintained for 17 days in vitro 3H]Dopamine basal outflow was enhanced by acetylcholine, nicotine, and atropine and was unaffected by oxotremorine, hexamethonium, and d-tubocurarine. The action of nicotine was antagonized by d-tubocurarine, and that of atropine was partially blocked by oxotremorine. A similar picture was seen when the influence of cholinergic agents was studied under depolarizing conditions. The action of oxotremorine was dependent on nerve activity. The presence of both muscarinic and nicotinic antagonists was necessary for abolishing the effect of acetylcholine on the dopamine outflow. These results show that dopamine release in both types of neuron-enriched cultures can be influenced by cholinergic agents and that both muscarinic and nicotinic receptors are involved in regulation of the amine's outflow.