Pregabalin and topiramate regulate behavioural and brain gene transcription changes induced by spontaneous cannabinoid withdrawal in mice
Pregabalin and topiramate regulate behavioural and brain gene transcription changes induced by spontaneous cannabinoid withdrawal in mice
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DOI：
10.1111/j.1369-1600.2011.00406.x
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发表时间：
2013-03-01
影响因子：
3.4
通讯作者：
Manzanares, Jorge
中科院分区：
文献类型：
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作者：
Aracil-Fernandez, Auxiliadora;Almela, Pilar;Manzanares, Jorge
本研究检查了普瑞巴林和托吡酯对小鼠自发大麻素戒断引起的行为和基因转录改变的作用。通过给小鼠施用CP-55，940（0.5mg/kg/12小时; i. p.; 7天）。通过在停止CP-55，940治疗后第1天和第3天测量运动活动、躯体体征和焦虑样行为，进行自发大麻素戒断的行为评估。在大麻素戒断的第13天，小鼠接受普瑞巴林（40 mg/kg/12小时; p.o.）或托吡酯（50 mg/kg/12小时; p.o.）并评估他们对戒断症状和焦虑样行为的反应。CP-55，940给药在第1天降低了直肠温度和运动活动。在大麻素给药中断后第1天，与对照组相比，运动活动和勃起次数增加。停止大麻素治疗诱导的类大麻行为在停药的第1天和第3天显著增加。普瑞巴林或托吡酯的管理阻断了运动的迹象，并显着减少焦虑样行为。大麻素戒断降低腹侧被盖区酪氨酸羟化酶（TH）基因表达和延髓核（NAcc）中μ阿片受体基因表达，并增加NAcc中CB 1受体基因表达。托吡酯或普瑞巴林可阻断大麻素戒断引起的TH下降和CB 1基因表达的增加。这两种药物都未能改变μ阿片受体基因的表达。这些结果表明，普瑞巴林和托吡酯可能导致与自发大麻素戒断相关的焦虑样行为和运动症状的治疗有用。
This study examined the actions of pregabalin and topiramate on behavioural and gene transcription alterations induced by spontaneous cannabinoid withdrawal in mice. Tolerance was induced in mice by administration of CP-55,940 (0.5mg/kg/12 hours; i.p.; 7 days). Behavioural assessment of spontaneous cannabinoid withdrawal was performed by measuring motor activity, somatic signs and anxiety-like behaviour on days 1 and 3 after cessation of treatment with CP-55,940. On days 13 of cannabinoid withdrawal, mice received pregabalin (40mg/kg/12 hours; p.o.) or topiramate (50mg/kg/12 hours; p.o.) and their actions on signs of withdrawal and anxiety-like behaviour were evaluated. The administration of CP-55,940 decreased rectal temperature and motor activity on day 1. On day 1 after interruption of cannabinoid administration, motor activity and the number of rearings increased compared with control group. Anxiety-like behaviour induced by cessation of cannabinoid treatment increased significantly on days 1 and 3 of withdrawal. The administration of pregabalin or topiramate blocked the motor signs and reduced significantly anxiety-like behaviour. Cannabinoid withdrawal decreased tyrosine hydroxylase (TH) gene expression in the ventral tegmental area and mu-opioid receptor gene expression in the nucleus accumbens (NAcc) and increased CB1 receptor gene expression in the NAcc. Treatment with topiramate or pregabalin blocked the decrease of TH and the increase of CB1 gene expressions induced by cannabinoid withdrawal. Both drugs failed to alter mu-opioid receptor gene expression. These results suggest that pregabalin and topiramate may result useful for the treatment of anxiety-like behaviour and motor symptoms associated with spontaneous cannabinoid withdrawal.