Zurita A, Murúa S, Molina V
Departamento de Farmacología, Universidad Nacional de Córdoba, Argentina.
Eur J Pharmacol. 1996 Mar 28;299(1-3):1-7. doi: 10.1016/0014-2999(95)00754-7.
This study assessed the effect of an uncontrollable stressor on the preference for a palatable solution (sucrose 1%), and on the preference for a context associated with a single administration of D-amphetamine (3 mg/kg i.p.) by means of the conditioning place preference test. We also evaluated the effect of prior naloxone (2 mg/kg, i.p.) administration on the influence of this stressful stimulus in both tests. Animals previously submitted to a 120-min--but not 60-min--restraint period showed a selective reduction in the preference for sucrose intake as compared to unstressed animals. Similarly, an identical restraint exposure elicited a diminished preference for the place previously paired with amphetamine. Both stress-induced effects were blocked by prior naloxone administration. These data demonstrate that a highly aversive experience decreased the reinforcing efficacy of sucrose and amphetamine, suggesting that uncontrollable stress may lead to an impaired capacity to experience pleasure, which could resemble the anhedonia observed in clinical depression. Furthermore, an endogenous opiate mechanism activated by stress seems to be involved in stress-induced anhedonia since naloxone normalized the reduction of the rewarding induced by both reinforcers.
本研究通过条件性位置偏爱试验,评估了不可控应激源对偏爱可口溶液(1%蔗糖)以及对与单次腹腔注射3毫克/千克D-苯丙胺相关环境的偏爱的影响。我们还评估了预先腹腔注射纳洛酮(2毫克/千克)对这两种试验中这种应激刺激影响的作用。与未受应激的动物相比,先前经历120分钟(而非60分钟)束缚期的动物对蔗糖摄入的偏爱选择性降低。同样,相同的束缚暴露使对先前与苯丙胺配对的位置的偏爱减弱。预先注射纳洛酮可阻断这两种应激诱导的效应。这些数据表明,高度厌恶的经历会降低蔗糖和苯丙胺的强化效力,提示不可控应激可能导致体验愉悦的能力受损,这可能类似于临床抑郁症中观察到的快感缺失。此外,应激激活的内源性阿片机制似乎参与了应激诱导的快感缺失,因为纳洛酮使两种强化物诱导的奖赏减少恢复正常。