Behavioural and biochemical effects in the adult rat after prolonged postnatal administration of clozapine

Psychopharmacology (Berl). 1983;81(3):239-43. doi: 10.1007/BF00427270.

Abstract

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.

MeSH terms

  • Animals
  • Apomorphine / pharmacology
  • Behavior, Animal / drug effects*
  • Body Weight / drug effects
  • Brain Chemistry / drug effects*
  • Clozapine / pharmacology*
  • Corpus Striatum / metabolism
  • Dibenzazepines / pharmacology*
  • Dopamine / metabolism
  • Homovanillic Acid / metabolism
  • Humans
  • Male
  • Motor Activity / drug effects
  • Rats
  • Rats, Inbred Strains
  • Reinforcement Schedule
  • Stereotyped Behavior / drug effects

Substances

  • Dibenzazepines
  • Clozapine
  • Apomorphine
  • Dopamine
  • Homovanillic Acid