[Behavioural effects of 8-OH-DPAT, a 5-HT1A agonist in rats and effects on the behaviour of antimanic drugs].

Effects of lithium, carbamazepine, zotepine, and clonazepam were examined on the behaviour mediated by 5-HT1A receptor and at 5-HT1A binding sites in rats. Forepaw treading, one component of 5-HT behavioural syndrome following subcutaneous injections of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), was not altered by reserpine, p-chlorophenylalanine, or alpha-methyl-p-tyrosine; in reserpine-treated rats, it was antagonized only by spiperone or by (-)-propranolol. These results indicate that 8-OH-DPAT-induced forepaw treading is produced by the direct stimulation of 5-HT1A receptor postsynaptically and also that this behaviour is not mediated by monoaminergic neurons. Lithium, carbamazepine, and zotepine inhibited forepaw treading in untreated rats; only lithium and clonazepam inhibited it in reserpine-treated rats. After 14 days treatment, only lithium enhanced it while its enhancement was abolished by reserpine. Radioligand binding studies using [3H]-8-OH-DPAT demonstrated that zotepine possessed weak affinity for 5-HT1A receptor; others lacked affinity. These results from acute experiments suggest that all drugs tested have inhibitory effects on the 5-HT1A receptor function. These effects, however, were not mediated by 5-HT1A receptor. And it is also suggested that the 5-HT1A receptor function after chronic lithium treatment might be enhanced by monoaminergic systems transsynaptically.