Ouachikh Omar, Dieb Wisam, Durif Franck, Hafidi Aziz
Clermont Université, Université d'Auvergne, EA7280, Laboratoire de Neuropsychopharmacologie des systèmes dopaminergiques sous corticaux, Clermont-Ferrand, France.
Clermont Université, Université d'Auvergne, EA7280, Laboratoire de Neuropsychopharmacologie des systèmes dopaminergiques sous corticaux, Clermont-Ferrand, France; CHU Clermont-Ferrand, Service de Neurologie, 63000 Clermont-Ferrand, France.
Behav Brain Res. 2014 Apr 1;262:1-7. doi: 10.1016/j.bbr.2013.12.021. Epub 2013 Dec 19.
Dopamine dysregulation syndrome in Parkinson's disease has been attributed to dopamine replacement therapies and/or a lesion of the dopaminergic system. Dopaminergic neuronal loss targets the substantia nigra and the ventral tegmental area (VTA). We hypothesize that dopamine replacement therapy is responsible for the potential reinforcement effect in Parkinson's disease, by acting on the neuronal reward circuitry. We previously demonstrated that the posterior (p) VTA, which projects to the nucleus accumbens (NAc), is implicated in the motivational effect of dopamine receptor agonists in 6-OHDA bilateral pVTA-lesioned drug-free animals. In the present study we investigated the implication of the anterior (a) VTA in the potential reinforcement effect of dopamine receptor agonists. Using the conditioned place preference (CPP) behavioral paradigm, we investigated the motivational effects of dopamine receptor agonists (bromocriptine and pramipexole), and cocaine in rats with a 6-OHDA bilateral lesion of the aVTA. Bromocriptine and pramipexole did not induce a significant CPP at 1mg/kg in both sham and bilateral 6-OHDA-lesioned rats. However bromocriptine induced CPP only at a dose of 3mg/kg in both animal groups. Moreover cocaine, which is known to increase dopamine release, induced reinforcing effects in both 6-OHDA-lesioned and sham rats. Our data show a lack of involvement of aVTA dopamine neurons in the motivational effects of bromocriptine, pramipexole and cocaine.
帕金森病中的多巴胺调节障碍综合征被认为与多巴胺替代疗法和/或多巴胺能系统损伤有关。多巴胺能神经元的丧失主要发生在黑质和腹侧被盖区(VTA)。我们推测,多巴胺替代疗法通过作用于神经元奖赏回路,在帕金森病中产生潜在的强化作用。我们之前证明,投射到伏隔核(NAc)的后(p)VTA,在6-OHDA双侧损毁且未用药的动物中,与多巴胺受体激动剂的动机效应有关。在本研究中,我们调查了前(a)VTA在多巴胺受体激动剂潜在强化作用中的影响。使用条件性位置偏爱(CPP)行为范式,我们研究了多巴胺受体激动剂(溴隐亭和普拉克索)以及可卡因对aVTA双侧6-OHDA损毁大鼠的动机效应。在假手术组和双侧6-OHDA损毁大鼠中,1mg/kg的溴隐亭和普拉克索均未诱导出显著的CPP。然而,在两个动物组中,溴隐亭仅在3mg/kg剂量时诱导出CPP。此外,已知能增加多巴胺释放的可卡因,在6-OHDA损毁大鼠和假手术组大鼠中均诱导出强化效应。我们的数据表明,aVTA多巴胺神经元未参与溴隐亭、普拉克索和可卡因的动机效应。