Repeated daily cocaine alters subsequent cocaine-induced increase of extracellular dopamine in the medial prefrontal cortex.
Repeated daily cocaine alters subsequent cocaine-induced increase of extracellular dopamine in the medial prefrontal cortex.
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发表时间：
1997-04
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通讯作者：
B. Sorg;Debra L. Davidson;P. Kalivas;B. Prasad
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作者：
B. Sorg;Debra L. Davidson;P. Kalivas;B. Prasad
将未经处理的雄性Sprague-Dawley大鼠或已经用5次每日盐水或可卡因注射（15 mg/kg i. p.）随后用注射可卡因进行攻击，并使用体内微透析测量内侧前额叶皮质（mPFC）中的细胞外多巴胺含量。可卡因的挑战增加细胞外多巴胺水平从基线在所有三组大鼠，但增加显着减少可卡因预处理组，与盐水预处理组相比。与此相反，mPFC多巴胺水平与系统性d-苯丙胺的挑战后，各组之间没有差异。为了测试重复的可卡因处理是否导致多巴胺从mPFC末端的释放能力改变，通过透析探针将KCl（10、30或100 mM）或d-苯丙胺（3、30或300 μ M）输注到mPFC中进行激发。在任何剂量下，两个治疗组之间的多巴胺水平均无差异。为了确定可卡因的作用是否由mPFC多巴胺末梢内的局部作用介导，通过微透析探针（1、10或100 μ M）给予可卡因激发。与全身性可卡因挑战相反，与盐水预处理对照组相比，在最低测试剂量下，可卡因局部输注引起每日可卡因预处理大鼠显著增加，在较高的两个剂量下无差异。总之，每日可卡因预处理的大鼠表现出抑制mPFC多巴胺反应随后全身，但不是局部，可卡因的挑战。结果表明，这种明显的耐受性是不是由于改变释放的多巴胺从mPFC终端，并可能依赖于改变传入调节中皮质多巴胺神经元。
Male Sprague-Dawley rats that were naive or that had been treated with five daily saline or cocaine injections (15 mg/kg i.p.) were subsequently challenged with an injection of cocaine, and extracellular dopamine content in the medial prefrontal cortex (mPFC) was measured using in vivo microdialysis. Cocaine challenge increased extracellular dopamine levels from base line in all three groups of rats, but the augmentation was significantly reduced in the cocaine-pretreated group, compared with the saline-pretreated group. In contrast, mPFC dopamine levels were not different among groups after challenge with systemic d-amphetamine. To test whether repeated cocaine treatment led to altered releasability of dopamine from mPFC terminals, challenge with KCI (10, 30 or 100 mM) or d-amphetamine (3, 30 or 300 microM) was made via infusion through the dialysis probe into the mPFC. No differences in dopamine levels were found between treatment groups for either drug at any dose. To determine whether the effects of cocaine were mediated by local actions within mPFC dopamine terminals, a cocaine challenge was administered through the microdialysis probe (1, 10 or 100 microM). In contrast to the systemic cocaine challenge, local infusion of cocaine elicited a significant increase in daily cocaine-pretreated rats, compared with saline-pretreated controls, at the lowest dose tested, with no differences at the higher two doses. In summary, daily cocaine-pretreated rats demonstrated a suppressed mPFC dopamine response to subsequent systemic, but not local, cocaine challenge. The results suggest that this apparent tolerance is not due to altered releasability of dopamine from mPFC terminals and may rely on altered afferent regulation of mesocortical dopamine neurons.