Neuroadaptations of total levels of adenylate cyclase, protein kinase A, tyrosine hydroxylase, cdk5 and neurofilaments in the nucleus accumbens and ventral tegmental area do not correlate with expression of sensitized or tolerant locomotor responses to cocaine
Neuroadaptations of total levels of adenylate cyclase, protein kinase A, tyrosine hydroxylase, cdk5 and neurofilaments in the nucleus accumbens and ventral tegmental area do not correlate with expression of sensitized or tolerant locomotor responses to cocaine
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DOI：
10.1111/j.1471-4159.2004.02891.x
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发表时间：
2005-02-01
影响因子：
4.7
通讯作者：
Wise, RA
中科院分区：
文献类型：
--
作者：
Hope, BT;Crombag, HS;Wise, RA
假设由高剂量可卡因治疗诱导的神经适应在药物治疗停止后持续存在，并介导对可卡因的敏感性和耐受性的表达。我们在接受更温和的行为有效可卡因治疗的大鼠中寻找这些神经适应的证据。将大鼠暴露于每天一次注射7次15 mg/kg可卡因的致敏方案或涉及连续输注相同日剂量的耐受性产生方案。我们评估了蛋白激酶A和腺苷酸环化酶的酶活性水平，酪氨酸羟化酶，cdk 5和神经丝的蛋白质水平在延髓核和腹侧被盖区。只有蛋白激酶A活性水平改变可卡因治疗，但这种改变只持续了7天，而敏化运动反应仍然是明显的，在21天。尽管在治疗结束后的第二天观察到对可卡因的行为耐受性，但在这一天或其他任何一天都没有改变分子测量。因此，虽然增加蛋白激酶A活性可以暂时调节可卡因的致敏反应，在我们的研究中评估的分子的总水平的改变不相关的表达致敏或耐受运动反应可卡因。
Neuroadaptations induced by high-dose cocaine treatment have been hypothesized to persist after the cessation of drug treatment and mediate the expression of sensitization and tolerance to cocaine. We looked for evidence of these neuroadaptations in rats receiving more modest behaviorally effective cocaine treatments. Rats were exposed to either a sensitizing regimen of seven once-daily injections of 15 mg/kg cocaine or a tolerance-producing regimen involving a continuous infusion of the same daily dose. We assessed enzyme activity levels of protein kinase A and adenylate cyclase, and protein levels of tyrosine hydroxylase, cdk5 and neurofilaments in the nucleus accumbens and ventral tegmental area. Only protein kinase A activity levels were altered by cocaine treatment, but this alteration persisted for only 7 days, whereas a sensitized locomotor response was still evident at 21 days. Although behavioral tolerance to cocaine was seen the day after the termination of treatment, none of the molecular measures was altered on this or any other day. Thus, although increased protein kinase A activity can temporarily modulate sensitized responses to cocaine, alterations in total levels of the molecules assessed in our study do not correlate with the expression of sensitized or tolerant locomotor responses to cocaine.