Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, POB 63 (Haartmaninkatu 8), FI-00014 University of Helsinki, Finland.
Neuroscience. 2011 Sep 29;192:312-21. doi: 10.1016/j.neuroscience.2011.07.004. Epub 2011 Jul 18.
A single administration of benzodiazepine-site ligands of the inhibitory GABA(A) receptors has been shown to lead to persistently potentiated AMPA receptor-mediated responses in dopaminergic neurons of the ventral tegmental area (VTA). This plasticity has been suggested to be a common property of different kinds of addictive drugs. We now wanted to test if the plasticity induced by diazepam would also affect behaviors elicited by other drugs of abuse. Activity and plasticity of the VTA dopaminergic neurons are known to be essential for the initiation and/or sensitization of the psychomotor responses to morphine and amphetamine. The effect of diazepam pre-treatment (a single dose of 5 mg/kg) was studied 24-72 h later in behaving C57BL/6J mice on locomotor activity induced by acute and repeated administration of morphine (5 mg/kg) and amphetamine (2.5 mg/kg). The pre-treatment attenuated the locomotor-activating effect of morphine. On the other hand, it reduced the amphetamine-induced locomotor sensitization in male mice in N-methyl-d-aspartate (NMDA) receptor-dependent manner. The acute amphetamine effect was not affected. The results indicate that benzodiazepine-induced neural plasticity transiently reduces the sensitivity to psychomotor stimulation by opioids and stimulants.
单次给予苯二氮䓬类药物（抑制性 GABA(A) 受体配体）可导致腹侧被盖区（VTA）多巴胺能神经元中 AMPA 受体介导的反应持续增强。这种可塑性被认为是不同类型成瘾药物的共同特性。我们现在想测试地西泮诱导的可塑性是否也会影响其他滥用药物引起的行为。众所周知，VTA 多巴胺能神经元的活动和可塑性对于吗啡和安非他命的精神运动反应的起始和/或敏化至关重要。在行为 C57BL/6J 小鼠中，研究了地西泮预处理（单次剂量 5mg/kg）对急性和重复给予吗啡（5mg/kg）和安非他命（2.5mg/kg）引起的运动活性的影响，24-72 小时后进行。预处理减弱了吗啡的运动激活作用。另一方面，它以 N-甲基-D-天冬氨酸（NMDA）受体依赖性方式减少雄性小鼠中安非他命引起的运动敏化。急性安非他命的作用不受影响。结果表明，苯二氮䓬类药物诱导的神经可塑性会短暂降低对阿片类药物和兴奋剂的精神运动刺激的敏感性。
