Abstract

Rationale Clozapine and the “atypical” antipsychotics are less prone than neuroleptics to induce extrapyramidal motor effects, worsening of the negative symptoms of schizophrenia and dysphoria. This is paralleled by preclinical evidence showing reduced suppression of behaviours aimed at the pursuit of reward, with increased measures of reward efficacy. Serotonin 5-HT2 receptors seem to play a role in determining this profile.
Objective We investigated the effects of clozapine on the microstructure of ingestive behaviour, which might reveal behavioural dimensions, such as reward evaluation and behavioural activation, which might be relevant in explaining its atypical profile. Moreover, we investigated the possibility that coadministration of the typical antipsychotic haloperidol and the 5-HT2A/2C receptor antagonist ritanserin might mimic clozapine effects.
Materials and methods The effects of clozapine (0.5, 1 and 5 mg/kg) and of the coadministration of haloperidol (0.05 mg/kg) and ritanserin (0.5 and 3 mg/kg) have been examined on the microstructure of licking for a 10% sucrose solution in rats.
Results Clozapine failed to affect whole ingestion as revealed by the lack of effect on lick number. However, it increased reward evaluation at the dose of 1 mg/kg, as revealed by increased mean bout size. Haloperidol resulted in a decreased bout size. Ritanserin failed to exert any effects either alone or when coadministered with haloperidol.
Conclusion The ability of clozapine to increase reward evaluation might contribute to explain its atypical profile both in the clinical setting and in preclinical studies. These results suggest that 5-HT2A/2C receptors are not involved in the observed effect.

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