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

• Published in: Journal of psychopharmacology (Oxford) 2012-09, Vol.26 (9), p.1231-1243
• Main Authors: den Boon, FS, Body, S, Hampson, CL, Bradshaw, CM, Szabadi, E, de Bruin, N
• Format: Article
• Language: English
• Subjects: Animals; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - adverse effects; Antipsychotic Agents - pharmacology; Aripiprazole; Behavior, Animal - drug effects; Clozapine; Clozapine - administration & dosage; Clozapine - adverse effects; Clozapine - pharmacology; Conditioning, Operant - drug effects; Dopamine Antagonists - administration & dosage; Dopamine Antagonists - adverse effects; Dopamine Antagonists - pharmacology; Dose-Response Relationship, Drug; Drugs; Female; Haloperidol; Haloperidol - administration & dosage; Haloperidol - adverse effects; Haloperidol - pharmacology; Kinetics; Mathematical models; Medical treatment; Models, Biological; Motor Activity - drug effects; Motor Skills - drug effects; Motor task performance; Neuroleptics; olanzapine; Operant conditioning; Piperazines - administration & dosage; Piperazines - adverse effects; Piperazines - pharmacology; Psychopharmacology; Psychotropic drugs; quetiapine; Quinolones - administration & dosage; Quinolones - adverse effects; Quinolones - pharmacology; Rats; Rats, Wistar; Reaction Time - drug effects; Reinforcement; Reinforcement Schedule; Rodents; Serotonin Antagonists - administration & dosage; Serotonin Antagonists - adverse effects; Serotonin Antagonists - pharmacology; Sulpiride - administration & dosage; Sulpiride - adverse effects; Sulpiride - analogs & derivatives; Sulpiride - pharmacology
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/0269881111421974

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.