Clozapine attenuates the locomotor sensitisation and the prepulse inhibition deficit induced by a repeated oral administration of Catha edulis extract and cathinone in rats

Abstract

Locomotor sensitisation and deficits in prepulse inhibition (PPI) induced by psychostimulants are two paradigms that have been widely studied as animal behavioural models of psychosis. Clozapine is one of the atypical antipsychotic agents which has been widely employed to reverse the aforementioned behavioural changes in these usual models. In this particular study, locomotor sensitisation and prepulse inhibition deficit were induced under the same context by intermittent oral administration of S-(−)-cathinone or Catha edulis extract in rats. The rats were then challenged by administration of the atypical antipsychotic drug, clozapine and were finally challenged with psychostimulants after 2-week of withdrawal. Locomotor activity and PPI were assessed and later analyses of the neurotransmitter levels were made. The results of this experiment show that repeated oral administration of cathinone or C. edulis extract enhanced locomotor and exploratory activity and lead to a gradual deficit in prepulse inhibition. This locomotor sensitisation and PPI deficit could be reversed by administration of clozapine. A challenge with psychostimulant on day 40 (i.e., after 2-week of withdrawal) resulted in a response similar to the initial exposure (day 1). Neurotransmitter level analyses showed a significant increase in the level of dopamine in the prefrontal cortex ( p < 0.05). There was also a significant decrease in the level of 5-hydroxytryptamine (5-HT) in the nucleus accumbens ( p < 0.05) and its metabolite, 5-hydroxyindole acetic acid (5-HIAA) in the prefrontal cortex ( p < 0.01). In the remaining regions (anterior and posterior striatum), there were no significant changes. In conclusion, this is the first study to demonstrate that repeated administration of C. edulis extract, or commercial cathinone, induces prepulse inhibition deficit and clozapine reverses both C. edulis or cathinone-induced sensitised locomotion and prepulse inhibition deficit.