Cocaine use and withdrawal prompt stress system responses. Stress and the negative affective state produced by cocaine withdrawal are major triggers for relapse. FKBP5 is a co-chaperone of the glucocorticoid receptor and regulates HPA axis negative feedback. The role of FKBP5 in cocaine-related behaviors has not been studied. The FKBP5 inhibitor SAFit2 was used to examine the role of FKBP5 in anxiety-like behavior during early cocaine withdrawal and in stress-induced reinstatement following cocaine self-administration in male and female rats. Withdrawal from cocaine self-administration resulted in heightened anxiety-like behavior in female rats, which was significantly attenuated by SAFit2 administration. SAFit2 pretreatment prior to stress-induced reinstatement to cocaine seeking significantly reduced active lever presses of males. In female rats, SAFit2 administration prevented stress-induced reinstatement for rats in metestrus or diestrus, but not proestrus or estrus phases at the time of reinstatement. These data suggest an important role for FKBP5 in stress-related behaviors following cocaine self-administration, particularly in females.

可卡因的使用和戒断提示压力系统做出反应。可卡因戒断所产生的压力和负面情感状态是复发的主要诱因。FKBP5是糖皮质激素受体的伴侣分子，可调节HPA轴负反馈。FKBP5在可卡因相关行为中的作用尚未研究。FKBP5抑制剂SAFit2用于检查FKBP5在可卡因早期戒断期间的焦虑样行为中以及在可卡因自用后在雄性和雌性大鼠中应激诱导的恢复中的作用。从可卡因自我给药中退出会导致雌性大鼠的焦虑样行为加剧，而通过SAFit2给药可明显减轻这种行为。SAFit2预处理在应力诱导的可卡因恢复之前进行，以寻求显着降低男性主动杠杆压力的方法。在雌性老鼠中 施用SAFit2可以防止应激的大鼠在肠肌或发情期恢复原状，但在恢复原状时不能阻止其发情期或发情期。这些数据表明FKBP5在可卡因自我给药后，尤其是女性中，在与压力相关的行为中起着重要作用。