Brain Health Institute and Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway 08854, United States.
Brain Health Institute and Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway 08854, United States.
Neurosci Lett. 2024 Jul 27;836:137888. doi: 10.1016/j.neulet.2024.137888. Epub 2024 Jun 28.
There are currently no FDA-approved treatments for cocaine use disorder. Recent preclinical and clinical studies showed that deep brain stimulation (DBS) in limbic regions reduced drug seeking behavior. Our previous work indicated that DBS of the nucleus accumbens shell attenuated reinstatement of cocaine seeking, a model of relapse, in male rats. The current experiments were designed to evaluate the effect of electrical DBS on cocaine reinstatement in female rats across the estrous cycle. Rats were allowed to self-administer cocaine and lever responding was subsequently extinguished. Cocaine seeking was reinstated by an acute injection of experimenter-delivered cocaine. The effect of nucleus accumbens shell DBS vs. sham stimulation on cocaine-primed reinstatement was evaluated in female and male rats using a within-subjects counterbalanced design. Consistent with previous work, accumbens shell DBS suppressed cocaine seeking in male rats. In sharp contrast, accumbens shell DBS had no effect on cocaine reinstatement in female rats evaluated in either the estrus or non-estrus phases. These results suggest that changes across the estrous cycle are not responsible for the differences in the effect of DBS on cocaine reinstatement between female and male rats.
目前，还没有获得 FDA 批准的可卡因使用障碍治疗方法。最近的临床前和临床研究表明，刺激边缘区域的深部脑刺激（DBS）可以减少药物寻求行为。我们之前的工作表明，刺激伏隔核壳部可以减轻雄性大鼠可卡因寻求的复燃，这是一种复发模型。目前的实验旨在评估电刺激 DBS 对雌性大鼠在整个发情周期中可卡因复燃的影响。大鼠被允许自行注射可卡因，随后消除杠杆反应。通过实验者给予的可卡因急性注射来恢复可卡因寻求。使用内部平衡设计，在雌性和雄性大鼠中评估了伏隔核壳部 DBS 与假刺激对可卡因引发复燃的影响。与之前的工作一致，伏隔核壳部 DBS 抑制了雄性大鼠的可卡因寻求。相比之下，在发情或非发情期，伏隔核壳部 DBS 对雌性大鼠可卡因复燃没有影响。这些结果表明，发情周期的变化并不是导致 DBS 对雌性和雄性大鼠可卡因复燃影响不同的原因。
