Abstract
The effect of pirenperone, a putative 5-HT 2 receptor antagonist, on various 5-HT-mediated behavioural responses has been examined. The head twitch response in mice. induced by administration of carbidopa (25 mg/kg) followed by 5-hydroxytryptophan (5-HTP) (200 mg/kg), was inhibited in a dose-dependent manner by pirenperone. with an ED 50 of 76 μg/kg. The appearance of head weaving, forepaw treading and hind-limb abduction, which followed the administration of tranylcypromine (5 mg/kg) plus l-tryptophan 100 mg/kg) or quipazine (50 mg/kg) to rats, was also inhibited by pretreatment with pirenperone (10μg/kg). Pirenperone did not alter the rate of 5-HT synthesis in the rat brain. Whilst pirenperone (100 μg/kg) did decrease methamphetamine-induced locomotor activity in rats, a dose of haloperidol producing a similar inhibition of this response did not alter the 5-HT-mediated behaviour. It is suggested, therefore, that the currently used 5-HT-induced behavioural models are 5-HT 2 receptor-mediated.
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