title: 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.
authors.affiliation: Psychopharmacology Section, Division of Psychiatry, University of Nottingham, Nottingham, UK.
authors.forename: F S
authors.initials: FS
authors.lastname: den Boon
authors.forename: S
authors.initials: S
authors.lastname: Body
authors.forename: C L
authors.initials: CL
authors.lastname: Hampson
authors.forename: C M
authors.initials: CM
authors.lastname: Bradshaw
authors.forename: E
authors.initials: E
authors.lastname: Szabadi
authors.forename: N
authors.initials: N
authors.lastname: de Bruin
mesh_terms: D000077582:Amisulpride; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000068180:Aripiprazole; D001522:Behavior, Animal / Q000187:drug effects; D003024:Clozapine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D007700:Kinetics; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects; D009048:Motor Skills / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012055:Reinforcement Schedule; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D013469:Sulpiride / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D010879:Piperazines; D015363:Quinolones; D012702:Serotonin Antagonists; D013469:Sulpiride; D000077582:Amisulpride; D000068180:Aripiprazole; D003024:Clozapine; D006220:Haloperidol