Peters Jamie, Vallone Joseph, Laurendi Kelly, Kalivas Peter W
Department of Neurosciences, Basic Science Building, Suite 403, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.
Psychopharmacology (Berl). 2008 Apr;197(2):319-26. doi: 10.1007/s00213-007-1034-2. Epub 2007 Dec 8.
The neural circuitry subserving cocaine-seeking after extinction vs abstinence alone requires different constituent brain structures. Spontaneous recovery of cocaine-seeking, a model, which incorporates both extinction and abstinence, depends on an unknown neural circuit.
The present study examined the hypothesis that the spontaneous recovery of cocaine-seeking would require overlapping but distinct neural circuits compared to models that incorporate either extinction or abstinence alone.
Rats were trained to self-administer cocaine (0.2 mg/inf), then responding on the cocaine-paired lever was extinguished, followed by an additional period of abstinence in the home cage. Finally, rats were returned to the self-administration context for a test of spontaneous recovery (SR TEST). Just before the SR TEST, discrete brain regions were inactivated with a GABA agonist cocktail (1 mM baclofen + 0.1mM muscimol) to determine the relative importance of these brain regions in the spontaneous recovery of cocaine-seeking.
The inactivation of the ventromedial prefrontal cortex (vPFC) enhanced cocaine-seeking, whereas the inactivation of the basolateral amygdala (BLA) attenuated spontaneous recovery. Inactivation of the nucleus accumbens core (Core) resembled the effects of BLA inactivation, but these results were confounded by an inhibitory effect of the vehicle treatment. Finally, the spontaneous recovery of cocaine-seeking was unaltered by manipulations of the dorsomedial prefrontal cortex (dPFC) and the nucleus accumbens shell (Shell).
The neural circuitry subserving cocaine-seeking behavior in a spontaneous recovery model requires the BLA and possibly the Core, like extinction models. In addition, this behavior is subject to regulation by vPFC, in a manner functionally opposite to that of the BLA.
与仅戒断相比，消退后寻求可卡因的神经回路需要不同的组成脑结构。寻求可卡因的自发恢复是一种结合了消退和戒断的模型，依赖于未知的神经回路。
本研究检验了这样一个假设，即与仅包含消退或戒断的模型相比，寻求可卡因的自发恢复需要重叠但不同的神经回路。
训练大鼠自我注射可卡因（0.2毫克/次注射），然后对与可卡因配对的杠杆的反应消退，随后在饲养笼中进行额外的戒断期。最后，将大鼠放回自我给药环境中进行自发恢复测试（SR测试）。就在SR测试前，用GABA激动剂混合物（1毫摩尔巴氯芬 + 0.1毫摩尔蝇蕈醇）使离散的脑区失活，以确定这些脑区在寻求可卡因的自发恢复中的相对重要性。
腹内侧前额叶皮层（vPFC）失活增强了对可卡因的寻求，而基底外侧杏仁核（BLA）失活减弱了自发恢复。伏隔核核心（Core）失活类似于BLA失活 的效果，但这些结果因载体处理的抑制作用而混淆。最后，背内侧前额叶皮层（dPFC）和伏隔核壳（Shell）的操作未改变可卡因寻求的自发恢复。
在自发恢复模型中，维持可卡因寻求行为的神经回路需要BLA，可能还需要Core，这与消退模型一样。此外，这种行为受到vPFC的调节，其方式在功能上与BLA相反。
