Ventral tegmental afferents in stress-induced reinstatement: the role of cAMP response element-binding protein.
Ventral tegmental afferents in stress-induced reinstatement: the role of cAMP response element-binding protein.
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DOI：
10.1523/jneurosci.2827-10.2010
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发表时间：
2010-12-01
期刊：
影响因子：
--
通讯作者：
Blendy JA
中科院分区：
文献类型：
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作者：
Briand LA;Vassoler FM;Pierce RC;Valentino RJ;Blendy JA
转录因子CREB是应激而不是药物诱导的可卡因条件性位置偏爱恢复所必需的。为了揭示与CREB依赖相关的神经回路，我们在腹侧被盖区(VTA)注射了逆行示踪剂，并在幼稚和可卡因条件作用的小鼠中识别了应激或可卡因暴露后激活的传入。在缺乏CREB的小鼠(CREBαΔ小鼠)中，在游泳应激6min后，终纹背核和腹床核(BNST)、外侧隔核(LS)和伏核(NAC)壳内神经元的Fos表达显著降低，但在可卡因暴露(20 mg/kg)后不明显。此外，CREBαΔ小鼠vBNST和下缘皮质(IL)中Vta传入神经元的激活在应激反应中被钝化。这种神经元激活模式在应激暴露前习惯于可卡因位置偏爱程序的小鼠中持续存在。此外，利多卡因灭活(0.4BNST，L，4%)的研究表明，在游泳应激诱导的可卡因条件性奖赏的恢复中，激活μ是必要的。综上所述，目前的研究表明，CREB是激活一个独特的环路所必需的，该环路汇聚在多巴胺奖赏通路上，导致药物奖赏的恢复，并指向BNST，作为应激和奖赏回路的关键交叉点。
The transcription factor CREB is required for stress- but not drug-induced reinstatement of cocaine conditioned place preference. To reveal the neural circuitry associated with this CREB dependence we injected a retrograde tracer into the ventral tegmental area (VTA) and identified afferents that were activated following stress or cocaine exposure in both naïve and cocaine conditioned mice. Neuronal activation, as assessed by Fos expression, was greatly reduced in the dorsal and ventral bed nucleus of the stria terminalis (BNST), lateral septum (LS), and nucleus accumbens (NAc) shell in mice lacking CREB (CREBαΔ mice) following a 6-min swim stress, but not following cocaine exposure (20mg/kg). Additionally, activation of VTA afferent neurons in the vBNST and the infralimbic cortex (IL) in CREBαΔ mice was blunted in response to stress. This pattern of neuronal activation persisted in mice that were conditioned to a cocaine place preference procedure prior to stress exposure. Furthermore, lidocaine inactivation (0.4μL, 4%) studies demonstrated the necessity of BNST activation for swim stress-induced reinstatement of cocaine-conditioned reward. Together, the present studies demonstrate that CREB is required for the activation of a unique circuit that converges on the dopamine reward pathway to elicit reinstatement of drug reward and points at the BNST as a key intersection between stress and reward circuits.