Nesbit Maya O, Dias Carine, Phillips Anthony G
Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 3402-2215 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada.
Behav Brain Res. 2017 Mar 15;321:223-231. doi: 10.1016/j.bbr.2016.12.043. Epub 2017 Jan 3.
Tetrahydroprotoberberines (THPB) have a high affinity for dopamine (DA) D1 and D2 receptors and may provide a novel treatment for drug addiction. We assessed the effects of the THPB d-govadine on the acquisition, expression, extinction and reinstatement of d-amphetamine-(1.5mg/kg, i.p.) induced conditioned place preference (CPP). Furthermore, the effects of d-govadine on conditioned association between contextual stimuli and a natural reward were examined using food-induced CPP. In separate experiments, rats received d-govadine (0, 0.5 or 1.0mg/kg, i.p.) before a) each d-amphetamine injection during conditioning, b) expression of amphetamine-induced CPP, c) each extinction session, d) amphetamine-induced reinstatement of CPP, or e) placement into a compartment containing food during conditioning. Although d-govadine had no effect on acquisition of amphetamine CPP, treatment with d-govadine during acquisition dose-dependently extinguished a preference for the amphetamine-associated context more quickly than vehicle treatment. Moreover, d-govadine treatment facilitated the extinction of amphetamine CPP when given repeatedly throughout the extinction phase. Although the expression of amphetamine CPP was not affected by d-govadine administered prior to the expression test, amphetamine-induced reinstatement of CPP following an extinction period was blocked by d-govadine (1.0mg/kg). The intermediate dose of d-govadine blocked the acquisition of food CPP, whereas the high dose facilitated extinction of this preference as compared to vehicle-treated animals. Therefore, d-govadine attenuates the maintenance of conditioned associations between contextual stimuli and amphetamine or food reward, as well as amphetamine-induced reinstatement of drug seeking behaviour. As such, d-govadine may be a candidate for further development as a pharmacological treatment of psychostimulant drug dependence.
四氢原小檗碱（THPB）对多巴胺（DA）D1和D2受体具有高亲和力，可能为药物成瘾提供一种新的治疗方法。我们评估了THPB d-戈瓦定对d-苯丙胺（1.5mg/kg，腹腔注射）诱导的条件性位置偏爱（CPP）的获得、表达、消退和恢复的影响。此外，使用食物诱导的CPP研究了d-戈瓦定对情境刺激与自然奖赏之间条件性关联的影响。在单独的实验中，大鼠在以下情况前接受d-戈瓦定（0、0.5或1.0mg/kg，腹腔注射）：a）条件反射训练期间每次注射d-苯丙胺前，b）苯丙胺诱导的CPP的表达，c）每次消退训练，d）苯丙胺诱导的CPP恢复，或e）条件反射训练期间放入装有食物的隔室前。尽管d-戈瓦定对苯丙胺CPP的获得没有影响，但在获得过程中用d-戈瓦定治疗比用赋形剂治疗能更迅速地剂量依赖性地消除对苯丙胺相关情境的偏爱。此外，在整个消退阶段反复给予d-戈瓦定治疗可促进苯丙胺CPP的消退。尽管在表达测试前给予d-戈瓦定对苯丙胺CPP的表达没有影响，但d-戈瓦定（1.0mg/kg）可阻断消退期后苯丙胺诱导的CPP恢复。d-戈瓦定的中间剂量可阻断食物CPP的获得，而高剂量与赋形剂处理的动物相比可促进这种偏爱的消退。因此，d-戈瓦定可减弱情境刺激与苯丙胺或食物奖赏之间条件性关联的维持，以及苯丙胺诱导的觅药行为恢复。因此，d-戈瓦定可能是作为精神兴奋剂药物依赖的药理学治疗进一步开发的候选药物。
