INHIBITION OF THE NICOTINIC ACETYLCHOLINE RESPONSE BY SEROTONERGIC AND MUSCARINIC AGENTS IN CHICK CILIARY GANGLION NEURONS

Chick ciliary ganglion neurones were investigated by whole cell voltage clamp recordings. The ACh- or nicotine-induced inward current was partially inhibited by perfusing the neurones with 5-HT. This effect was rapid ) less-than-or-equal-to 1 min), dose-dependent (50-1000 muM) and quickly reversible. The selective 5-HT1A agonist 8-OH-DPAT (10 muM) reduced the nicotinic ACh response more potently, irrespective of the absence or presence of propranolol (1 muM), a known 5-HT1A antagonist. Other serotonergic antagonists, like ICS 205-930 (1 muM), mianserin (10 muM) and methysergide (10 muM), also failed to antagonize the 5-HT-mediated decrease in the nicotinic response. Muscarine (50 muM) did not affect the nicotine-induced inward current but the muscarinic agonist oxotremorine (10 muM) also decreased the nicotine-induced inward current. Atropine, at small concentrations failed to block this effect but caused some reduction of the ACh response itself at larger (1-10 muM) concentrations. It is suggested that 5-HT may modulate synaptic transmission in ciliary ganglion neurones in vivo, The site of action of 5-HT, oxotremorine and atropine might be at or close to the ACh receptor complex, because of the fast onset and reversibility of the effects and lack of specificity for structurally different drugs.