Effects of daily chlorpromazine administration on behavioural and physiological parameters in the rat

Chlorpromazine is a classical neuroleptic drug which produces both therapeutic effects as well as unwanted side effects in human such as sedation, autonomic, endocrine and neurological effects. It is thought that blockade of dopamine D-2 receptors caused by chlorpromazine induces these untoward side effects. Pre-clinical studies on catalepsy has been proposed as an animal model for neuroleptic induced extrapyramidal side effects. The drug also blocks certain stereotypic behaviours in animals induced by dopamine agonists such as apomorphine and amphetamine. These stereotypic behaviours are circling, chewing, rearing, grooming and hyperactivity. Daily administration of chlorpromazine (1, 3 and 10 mg/kg, i.p) to rats for 21 days induced catalepsy, tolerance to catalepsy and locomotor sensitization following PCP (10 mg/kg, i.p) challenge. These results suggest that daily chlorpromazine treatment induced DA/NMDA-receptor sensitization to total locomotor activity following PCP challenge. Furthermore, there were no changes in other behavioural parameters assessed. Surprisingly daily chlorpromazine administration in rats also produced no changes in other physiological parameters assessed (body weight, food and water intake).