Effects of amisulpride and aripiprazole on progressive-ratio schedule performance: comparison with clozapine and haloperidol

Abstract

Clozapine and some other atypical antipsychotics (e.g. quetiapine, olanzapine) have been found to exert a characteristic profile of action on operant behaviour maintained by progressive-ratio schedules, as revealed by Killeen’s Mathematical Principles of Reinforcement model of schedule-controlled behaviour. These drugs increase the value of a parameter that expresses the ‘incentive value’ of the reinforcer (a) and a parameter that is inversely related to the organism’s ‘motor capacity’ (δ). This experiment examined the effects of two further atypical antipsychotics, aripiprazole and amisulpride, on progressive-ratio schedule performance in rats; the effects of clozapine and a conventional antipsychotic, haloperidol, were also examined. In agreement with previous findings, clozapine (4, 8 mg kg⁻¹) increased a and δ, whereas haloperidol (0.05, 0.1 mg kg⁻¹) reduced a and increased δ. Aripiprazole (3,30 mg kg⁻¹) increased δ but did not affect a. Amisulpride (5, 50 mg kg⁻¹) had a delayed and protracted effect: δ was increased 3–6 hours after treatment; a was increased 1.5 hours, and reduced 12–24 hours after treatment. Interpretation based on Killeen’s model suggests that aripiprazole does not share clozapine’s ability to enhance reinforcer value. Amisulpride produced a short-lived enhancement, followed by a long-lasting reduction, of reinforcer value. Both drugs impaired motor performance.