Psychopharmacology Section, Division of Psychiatry, University of Nottingham, Nottingham, UK.
J Psychopharmacol. 2012 Sep;26(9):1231-43. doi: 10.1177/0269881111421974. Epub 2011 Oct 3.
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.
氯氮平及其他一些非典型抗精神病药(如喹硫平、奥氮平)被发现对操作性行为具有特征性的作用模式,这通过 Killeen 的强化程序控制行为的数学原理模型得以揭示。这些药物增加了一个参数的值,该参数表示强化物的“激励值”(a)和一个与生物体的“运动能力”(δ)成反比的参数。本实验研究了另外两种非典型抗精神病药,阿立哌唑和氨磺必利,对大鼠递增比率程序表现的影响;还研究了氯氮平和一种传统抗精神病药,氟哌啶醇的影响。与先前的发现一致,氯氮平(4、8mg/kg)增加了 a 和 δ,而氟哌啶醇(0.05、0.1mg/kg)降低了 a 并增加了 δ。阿立哌唑(3、30mg/kg)增加了 δ,但没有影响 a。氨磺必利(5、50mg/kg)具有延迟和持久的作用:治疗后 3-6 小时增加 δ;a 增加 1.5 小时,12-24 小时后减少。基于 Killeen 模型的解释表明,阿立哌唑不具有增强强化物价值的氯氮平的能力。氨磺必利产生短暂的增强,随后是强化物价值的持久降低。这两种药物都损害了运动表现。