Hakan R L, Hart C, Eyl C
Department of Psychology, University of North Carolina at Wilmington 28401.
Synapse. 1993 Nov;15(3):191-7. doi: 10.1002/syn.890150304.
Extracellular recordings of single neurons within the nucleus accumbens (NAS) of halothane-anesthetized rats have revealed that systemic nicotine injections (0.5 and 1.0 mg/kg, s.c.) inhibit the action potentials of normally inactive NAS neurons, evoked by fimbria stimulation (fimbria-driven responses, n = 18). These nicotine inhibitions of fimbria-driven NAS action potentials appear to be centrally mediated because they were reversed by subsequent systemic injections of the centrally acting nicotinic acetylcholine (nAch) antagonist, mecamylamine (1.0 mg/kg, s.c., n = 6) but not by the peripherally acting nAch antagonist, hexamethonium (2.0 mg/kg, s.c., n = 6). Fimbria-driven NAS neurons were also tested with morphine (2.5 mg/kg, s.c.) in some experiments. Consistent with many past observations (Hakan et al., 1989), morphine did not affect these driven neurons. In other experiments, nicotine-induced inhibition of NAS fimbria-driven units was followed by haloperidol (0.5 mg/kg, s.c.), in attempts to reveal the possible role of dopamine in these effects. Haloperidol was successful at reversing nicotine inhibitions in only some cases (n = 2/6). Thus, the role of dopamine in these NAS responses to nicotine remains unclear. In contrast to the fimbria-driven NAS responses, spontaneously active NAS neurons were not affected by nicotine injections yet were subsequently inhibited with systemic morphine. These results suggest a specific neuropharmacological organization in the region of the nucleus accumbens that may relate to the qualitative and subjective differences in the experimental effects of different psychoactive drugs. Iontophoretic studies designed to localize further the site of these nicotine effects on NAS neurons are in progress.
对氟烷麻醉的大鼠伏隔核（NAS）内单个神经元进行的细胞外记录显示，全身注射尼古丁（0.5和1.0mg/kg，皮下注射）可抑制由穹窿刺激诱发的正常无活性NAS神经元的动作电位（穹窿驱动反应，n = 18）。尼古丁对穹窿驱动的NAS动作电位的这些抑制作用似乎是由中枢介导的，因为随后全身注射中枢作用的烟碱型乙酰胆碱（nAch）拮抗剂美加明（1.0mg/kg，皮下注射，n = 6）可逆转这些抑制作用，但外周作用的nAch拮抗剂六甲双铵（2.0mg/kg，皮下注射，n = 6）则不能。在一些实验中，还用吗啡（2.5mg/kg，皮下注射）对穹窿驱动的NAS神经元进行了测试。与过去的许多观察结果一致（哈坎等人，1989年），吗啡对这些驱动神经元没有影响。在其他实验中，在尼古丁诱导对NAS穹窿驱动单位的抑制作用之后注射氟哌啶醇（0.5mg/kg，皮下注射），试图揭示多巴胺在这些作用中的可能作用。氟哌啶醇仅在某些情况下（n = 2/6）成功逆转了尼古丁的抑制作用。因此，多巴胺在这些NAS对尼古丁的反应中的作用仍不清楚。与穹窿驱动的NAS反应相反，自发活动的NAS神经元不受尼古丁注射的影响，但随后会被全身注射吗啡抑制。这些结果表明伏隔核区域存在特定的神经药理学组织，这可能与不同精神活性药物实验效果的质和主观差异有关。旨在进一步定位这些尼古丁对NAS神经元作用部位的离子电渗法研究正在进行中。
