Effect of 5-hydroxytryptamine on [3H]-acetylcholine release from guinea-pig striatal slices.

1. The effect of 5-hydroxytryptamine (5-HT) on spontaneous and electrically-evoked tritium efflux was studied in guinea-pig caudate nucleus slices preloaded with [3H]-choline. 2. 5-HT, 10-300 mumol l-1, temporarily increased the spontaneous tritium efflux (as well as the endogenous acetylcholine (ACh) release) and, after 15 min perfusion, inhibited it. The facilitatory effect of 5-HT on spontaneous efflux was increased while the inhibitory effect did not occur in slices taken from dopamine-depleted guinea-pigs. 3. The increase in spontaneous tritium efflux by 5-HT was blocked by methiothepin, methysergide (pA2 8.7) and by the selective 5-HT2 antagonist, ritanserin (pA2 6.7). 4. The inhibition of spontaneous tritium efflux by 5-HT was prevented by methysergide and methiothepin but not by ritanserin and (-)-propranolol. 5. 5-HT, 100 mumol l-1, inhibited the electrically-evoked tritium efflux and this effect was unchanged in dopamine-depleted slices. 6. The inhibition of electrically-evoked tritium efflux by 5-HT was blocked by methiothepin and methysergide but not by (-)-propranolol or ritanserin. 7. These results suggest that 5-HT may exert a rapid and transient (excitatory) and a more prolonged (inhibitory) control over striatal cholinergic neurones.