Hildebrand B E, Svensson T H
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
J Neural Transm (Vienna). 2000;107(8-9):861-72. doi: 10.1007/s007020070038.
Recently we have shown that the nicotinic receptor (nAChR) antagonist mecamylamine both when administered systemically and locally into the ventral tegmental area (VTA) to chronically nicotine-treated rats reduces dopamine (DA) output in the nucleus accumbens (NAC) and elicits behavioral withdrawal signs. However, the putative contributory role of nAChRs in the NAC in mediating these effects of systemic mecamylamine has not been clarified. Therefore, we here investigated the effect on extracellular levels of DA in the NAC of local intraaccumbal administration of mecamylamine to chronically nicotine-treated rats and its putative behavioral correlates. In these experiments local application of mecamylamine into the NAC, in a concentration that increased NAC DA levels in control rats, did not affect DA output or behavior in the nicotine-treated animals. These results provide further support for the contention that nAChRs in the VTA, but not in the NAC, are of major importance for the mesolimbic DA reduction and associated behavioral signs in nicotine withdrawal.
最近我们发现,烟碱型受体(nAChR)拮抗剂美加明,无论是全身给药还是局部注入腹侧被盖区(VTA),对长期接受尼古丁治疗的大鼠而言,均可降低伏隔核(NAC)中的多巴胺(DA)释放,并引发行为戒断症状。然而,NAC中的nAChRs在介导美加明全身给药的这些效应中所假定的作用尚未明确。因此,我们在此研究了向长期接受尼古丁治疗的大鼠伏隔核局部注射美加明对NAC中DA细胞外水平的影响及其假定的行为相关性。在这些实验中,向NAC局部应用美加明,其浓度可增加对照大鼠的NAC DA水平,但对接受尼古丁治疗的动物的DA释放或行为没有影响。这些结果进一步支持了以下观点:VTA而非NAC中的nAChRs对于中脑边缘DA减少及尼古丁戒断相关行为症状至关重要。