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 μmol1−1, 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 μmol1−1, 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.