Laboratory of Pharmacology, Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, Univ. Estadual Paulista - UNESP, Araraquara, SP 14801-902, Brazil; Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, US National Institutes of Health, Department of Health and Human Services, Baltimore, MD, USA.
Neuroscience. 2013 Dec 3;253:29-39. doi: 10.1016/j.neuroscience.2013.08.034. Epub 2013 Aug 29.
Neural plasticity has been observed in the bed nucleus of the stria terminalis (BNST) following exposure to both cocaine and androgenic-anabolic steroids. Here we investigated the involvement of the BNST on changes in cardiovascular function and baroreflex activity following either single or combined administration of cocaine and testosterone for 10 consecutive days in rats. Single administration of testosterone increased values of arterial pressure, evoked rest bradycardia and reduced baroreflex-mediated bradycardia. These effects of testosterone were not affected by BNST inactivation caused by local bilateral microinjections of the nonselective synaptic blocker CoCl2. The single administration of cocaine as well as the combined treatment with testosterone and cocaine increased both bradycardiac and tachycardiac responses of the baroreflex. Cocaine-evoked baroreflex changes were totally reversed after BNST inactivation. However, BNST inhibition in animals subjected to combined treatment with cocaine and testosterone reversed only the increase in reflex tachycardia, whereas facilitation of reflex bradycardia was not affected by local BNST treatment with CoCl2. In conclusion, the present study provides the first direct evidence that the BNST play a role in cardiovascular changes associated with drug abuse. Our findings suggest that alterations in cardiovascular function following subchronic exposure to cocaine are mediated by neural plasticity in the BNST. The single treatment with cocaine and the combined administration of testosterone and cocaine had similar effects on baroreflex activity, however the association with testosterone inhibited cocaine-induced changes in the BNST control of reflex bradycardia. Testosterone-induced cardiovascular changes seem to be independent of the BNST.
神经可塑性已在终纹床核（BNST）中观察到，这是在接触可卡因和雄激素 - 合成代谢类固醇后发生的。在这里，我们研究了 BNST 在连续 10 天给予可卡因和睾丸酮单一或联合给药后心血管功能和压力反射活动变化中的作用。睾丸酮的单次给药增加了动脉压值，引起静息心动过缓，并减少了压力反射介导的心动过缓。BNST 用非选择性突触阻滞剂 CoCl2 双侧局部微注射失活并未影响睾丸酮的这些作用。可卡因的单次给药以及与睾丸酮和可卡因联合治疗均增加了压力反射的心动过缓和心动过速反应。BNST 失活后，可卡因引起的压力反射变化完全逆转。然而，在接受可卡因和睾丸酮联合治疗的动物中，BNST 抑制仅逆转了反射性心动过速的增加，而局部 BNST 用 CoCl2 处理并未影响反射性心动过缓的促进。总之，本研究首次提供了直接证据，证明 BNST 在与药物滥用相关的心血管变化中起作用。我们的研究结果表明，亚慢性暴露于可卡因后心血管功能的改变是由 BNST 中的神经可塑性介导的。可卡因的单次治疗和睾丸酮和可卡因联合给药具有相似的压力反射活动作用，但是与睾丸酮的关联抑制了 BNST 对反射性心动过缓的可卡因诱导变化。睾丸酮引起的心血管变化似乎与 BNST 无关。
