Amalric M, Koob G F
Pharmacol Biochem Behav. 1985 Sep;23(3):411-5. doi: 10.1016/0091-3057(85)90014-0.
The effect of microinjection of a quaternary opiate antagonist methylnaloxonium (MN) in the lateral ventricle, ventral tegmental area (VTA) and nucleus accumbens (N.Acc.) was examined on the locomotor activation produced by a subcutaneous heroin injection (0.5 mg/kg) in the rat. At this dose heroin typically produced an initial depressant phase (0-30 min) followed by a prolonged hyperactivity (40-120 min). Lateral ventricular injections did not significantly reverse the initial depressant effects of heroin (0-30 min), and a dose of 4 micrograms was needed to reverse the subsequent hyperactivity (40-120 min). The most potent blockade was observed following injections into the N.Acc. where 0.1 microgram significantly reversed the initial depressant effects of heroin (0-30 min), and 0.25 microgram significantly reversed the subsequent hyperactivity (40-120 min). In the VTA, MN had the weakest effects, failing to reverse significantly the initial depressant effects of heroin (0-30 min), and only attenuating the subsequent hyperactivity at the highest doses. It is suggested that certain opiates act on the mesolimbic dopaminergic pathway at the level of the cell bodies in the VTA, but more critically in the N.Acc., possibly on opiate receptors postsynaptic to the dopamine neurons.
研究了向大鼠侧脑室、腹侧被盖区（VTA）和伏隔核（N.Acc.）微量注射季铵类阿片拮抗剂甲基纳洛酮（MN）对皮下注射海洛因（0.5mg/kg）所致运动激活的影响。在此剂量下，海洛因通常会产生一个初始抑制期（0 - 30分钟），随后是长时间的多动期（40 - 120分钟）。侧脑室注射并不能显著逆转海洛因的初始抑制作用（0 - 30分钟），需要4微克的剂量才能逆转随后的多动（40 - 120分钟）。向N.Acc.注射后观察到最有效的阻断作用，其中0.1微克可显著逆转海洛因的初始抑制作用（0 - 30分钟），0.25微克可显著逆转随后的多动（40 - 120分钟）。在VTA中，MN的作用最弱，不能显著逆转海洛因的初始抑制作用（0 - 30分钟），仅在最高剂量时减弱随后的多动。提示某些阿片类药物作用于中脑边缘多巴胺能通路，作用于VTA中细胞体水平，但更关键的是在N.Acc.，可能作用于多巴胺神经元突触后的阿片受体。
