Behavioural and biochemical effects in the adult rat after prolonged postnatal administration of clozapine.
Rats were administered 10 mg/kg SC of clozapine (C) or vehicle solution (S) daily from day 1 after birth until 20 days of age. At 60 days of age (40 days after the postnatal treatment with C or S was interrupted) the stereotyped behaviour and the effects on locomotor activity elicited by apomorphine in S- and C-pretreated rats were investigated. The intensity of stereotyped behaviour as well as the decrement in locomotion induced by apomorphine (0.5--1 mg/kg SC) were not influenced by chronic C administration during development. Finally, at 80 days of age (60 days after the postnatal treatment with C or S was interrupted) rats were subjected to a differential reinforcement of low rates schedule (DRL15s). The results indicate that the acquisition of the DRL task performance criterion (Rs/Rf less than or equal to 2.5) was significantly more rapid in S-pretreated rats than in C-pretreated ones. In parallel biochemical experiments, homovanillic acid (HVA) content was measured in striatum in rats at 60 days of age (40 days after the postnatal treatment with C or S was interrupted). The results indicate that even if an acute challenge dose of 10 mg/kg C shows a certain degree of tolerance a single dose of 20 mg/kg C is still able to increase striatal HVA concentration in chronic C-pretreated animals. These data indicate that early postnatal administration of a non-cataleptogenic neuroleptic, like C, induces, in the adult rat, behavioural and biochemical changes which significantly differ from those elicited by a cataleptogenic neuroleptic, like haloperidol.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D003024:Clozapine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism; D003984:Dibenzazepines / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012055:Reinforcement Schedule; D013239:Stereotyped Behavior / Q000187:drug effects
D003984:Dibenzazepines; D003024:Clozapine; D001058:Apomorphine; D004298:Dopamine; D006719:Homovanillic Acid