Effect of quipazine, a serotonin-like drug, on striatal cholinergic interneurones

Quipazine (30 mg/kg i.p., 60 min), a serotonin-like drug increased ACh levels in the striatum (37%) but was without effect on the transmitter content in the hippocampus and the parietal cortex of the rat. Added in vitro(10(-5) M) or injected in vivo, quipazine did not affect choline acetylase and cholinesterase activities in striatal tissue. The drug effect on striatal ACh levels did not appear to be related to an interaction with dopamine metabolism. Indeed quipazine still increased striatal ACh levels after degeneration of the dopaminergic neurons had been induced by local injection of 6-OH-DA. p-Chlorophenylalanine (PCPA) pretreatment (300 mg/kg, 48 and 24 h before the experiment) definitely prevented the quipazine effect on ACh levels. This result suggested that the drug may partially act by its interference with 5-HT metabolism. 5-Methoxy-N,N-dimethyltryptamine (10 mg/kg, i.p., 30 min), a serotonergic agonist, induced a weak but significant increase in ACh levels. These data provide some preliminary evidence for the existence of an inhibitory control of the cholinergic interneurones by the serotonergic neurones projecting to the striatum. However, the lack of effect of 5-hydroxytryptophan (100 mg/kg i.p.), PCPA (2 x 300 mg/kg i.p.) and of Lilly 110 140 (10 mg/kg i.p.) and chlorimipramine (10 mg/kg i.p.), two potent inhibitors of 5-HT uptake, on striatal ACh levels indicate that further experiments are required to retain this hypothesis.