Hayase T, Yamamoto Y, Yamamoto K
Department of Legal Medicine, Kyoto University Graduate School of Medicine, Faculty of Medicine, Kyoto, Japan.
Behav Pharmacol. 2005 Sep;16(5-6):395-404. doi: 10.1097/00008877-200509000-00012.
As persistent behavioural changes, such as increased anxiety-related behaviours, can be predicted based on the phenomenon of psychostimulant-induced neuronal plasticity, the time course (3-, 5- and 10-day time points) of the effects of both a single and repeated (daily for 7 days) i.p. administrations of cocaine (COC) and methamphetamine (MA) on anxiety-related behavioural symptoms in the elevated plus-maze test were examined in mice. Furthermore, based on the reported interactions between brain dopamine versus cannabinoid (CB) receptors and the contribution of CB receptors to the occurrence of persistent anxiety-related behavioural symptoms, the interactions of the agonist CP 55940 (CP) and the endogenous ligands anandamide (arachidonylethanolamide: AEA), 2-arachidonylglycerol (ARA), N-arachidonyldopamine (NADA), noladin ether (NL), and virodhamine (VA) with the COC- or MA-induced anxiety-related behaviours were also studied. In both an acute experiment using a single COC (30 mg/kg) or MA (4 mg/kg) dose and a chronic experiment using repeated COC (15 mg/kg) or MA (2 mg/kg) doses, anxiety-related behavioural symptoms were observed similarly at 3- and 5-day time points, but disappeared at the 10-day time point. Among the CB ligands, the agonists CP, AEA, ARA, NADA, and NL provided strong protective effects against each parameter at 3- and 5-day time points. Therefore, it was concluded that both COC and MA caused persistent anxiety-related behavioural symptoms following both a single and repeated treatments. Since these anxiogenic effects were attenuated by the endogenous CB agonists, the involvement of brain CB receptors was suspected.
由于基于精神兴奋剂诱导的神经元可塑性现象可以预测持续的行为变化，如焦虑相关行为增加，因此研究了单次和重复（连续7天）腹腔注射可卡因（COC）和甲基苯丙胺（MA）对小鼠高架十字迷宫试验中焦虑相关行为症状的影响的时间进程（3天、5天和10天时间点）。此外，基于报道的脑多巴胺与大麻素（CB）受体之间的相互作用以及CB受体对持续焦虑相关行为症状发生的作用，还研究了激动剂CP 55940（CP）与内源性配体花生四烯乙醇胺（花生四烯酸乙醇酰胺：AEA）、2-花生四烯酸甘油（ARA）、N-花生四烯多巴胺（NADA）、诺拉汀醚（NL）和维罗达姆胺（VA）与COC或MA诱导的焦虑相关行为的相互作用。在使用单次COC（30 mg/kg）或MA（4 mg/kg）剂量的急性实验以及使用重复COC（15 mg/kg）或MA（2 mg/kg）剂量的慢性实验中，在3天和5天时间点类似地观察到焦虑相关行为症状，但在10天时间点消失。在CB配体中，激动剂CP、AEA、ARA、NADA和NL在3天和5天时间点对每个参数都提供了强大的保护作用。因此，得出结论，单次和重复治疗后，COC和MA均会导致持续的焦虑相关行为症状。由于这些致焦虑作用被内源性CB激动剂减弱，因此怀疑脑CB受体参与其中。
