Guyon A, Assouly-Besse F, Biala G, Puech A J, Thiébot M H
INSERM U-302, Département de Pharmacologie, Faculté de Médecine Pitié-Salpêtriére, Paris, France.
Psychopharmacology (Berl). 1993;110(4):460-6. doi: 10.1007/BF02244653.
Numerous data support the hypothesis that dopamine (DA) plays a crucial role in reward-related processes and in incentive learning in animals and man. The possibility that various neuroleptics exhibiting a high affinity for the dopaminergic D2 (and D3) receptors could reinforce DA transmission was studied using the conditioned place preference paradigm (CPP) in rats. This was done by examining the ability of these compounds to potentiate the reinforcing properties of food in hungry rats subjected to a version of the CPP paradigm which consisted of repeated pairings of food with a single environmental cue, the floor texture of an open field. During the test session when food was no longer available in the open field, the increase in the time spent by drug-free rats on the food-paired texture was assumed to indicate the perceived rewarding value of the food. This time was significantly lengthened when the specific D2 (D3)-receptor antagonists sulpiride (4 mg/kg), amisulpride (0.5, 1 mg/kg) or pimozide (0.03, 0.06 mg/kg) were administered before the food conditioning sessions. Larger doses of these compounds as well as haloperidol, metoclopramide and the non-specific D1-D2 antagonist, chlorpromazine, regardless of the doses tested, did not exhibit this effect, but rather reduced the food-induced CPP, an action usually associated with neuroleptics. The positive effects of amisulpride was reversed by a D1 receptor antagonist, SCH 23390 (0.01 mg/kg). These results suggest that, as with amphetamine (0.5 mg/kg), some D2-specific neuroleptics enhance the incentive value of food in a narrow range of low doses, an effect proposed to reflect a "prohedonic" property.(ABSTRACT TRUNCATED AT 250 WORDS)
大量数据支持这样一种假说,即多巴胺(DA)在动物和人类与奖励相关的过程以及动机学习中起着至关重要的作用。利用大鼠的条件性位置偏爱范式(CPP),研究了对多巴胺能D2(和D3)受体具有高亲和力的各种抗精神病药物增强DA传递的可能性。这是通过检测这些化合物增强饥饿大鼠食物强化特性的能力来实现的,这些大鼠接受了一种CPP范式,该范式包括将食物与单一环境线索(开放场地的地面纹理)反复配对。在测试阶段,当开放场地不再提供食物时,未用药大鼠在与食物配对的纹理上花费时间的增加被认为表明了食物的感知奖励价值。当在食物条件化训练前给予特异性D2(D3)受体拮抗剂舒必利(4mg/kg)、阿立哌唑(0.5、1mg/kg)或匹莫齐特(0.03、0.06mg/kg)时,这段时间显著延长。这些化合物以及氟哌啶醇、甲氧氯普胺和非特异性D1-D2拮抗剂氯丙嗪的较大剂量,无论测试剂量如何,均未表现出这种效果,反而降低了食物诱导的CPP,这是抗精神病药物通常具有的作用。阿立哌唑的积极作用被D1受体拮抗剂SCH 23390(0.01mg/kg)逆转。这些结果表明,与苯丙胺(0.5mg/kg)一样,一些D2特异性抗精神病药物在低剂量的狭窄范围内增强了食物的动机价值,这种作用被认为反映了一种“享乐前”特性。(摘要截短于250字)