Levy A D, Rittenhouse P A, Li Q, Yracheta J, Kunimoto K, Van de Kar L D
Department of Pharmacology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153.
Psychopharmacology (Berl). 1994 Jan;113(3-4):547-54. doi: 10.1007/BF02245238.
Previous studies have determined that chronic cocaine exposure inhibits the serotonergic stimulation of hormone secretion. The present experiments were conducted to determine whether the endocrine responses to stress could be a useful approach to assess the influence of cocaine exposure on neuronal function. Male rats received twice daily injections of cocaine (1-15 mg/kg, IP) for 7 days. Animals were subsequently exposed to different stressors, i.e. conditioned emotional stress utilizing a low (0.5 mA) or high (1.5 mA) intensity footshock during training, or to immobilization stress. Immediately after the stress procedures, blood samples were collected for radioimmunoassay of plasma corticosterone, prolactin, and renin concentrations. Repeated cocaine exposure attenuated the stress-induced elevations of corticosterone and prolactin secretion, and attenuated some of the behavioral effects of the low intensity conditioned emotional stress. When exposed to the high intensity conditioned emotional stress, cocaine did not alter the endocrine or behavioral effects of stress. Finally, repeated cocaine exposure modified the immobilization stress-induced elevation of renin secretion; low doses of cocaine (1 or 5 mg/kg) attenuated, while higher doses (10 mg/kg) potentiated the renin response to immobilization stress. Thus, the influence of repeated cocaine exposure on the endocrine and behavioral responses to stress appears to depend upon the type and intensity of the stressor. Compared with previous studies which found altered neuroendocrine responses to serotonin releasers and agonists following cocaine exposure, the hormonal responses to stress are less consistently modified by cocaine.
以往的研究已经确定，长期接触可卡因会抑制血清素对激素分泌的刺激作用。本实验旨在确定对应激的内分泌反应是否可能是评估可卡因暴露对神经元功能影响的一种有用方法。雄性大鼠每天接受两次可卡因注射（1 - 15毫克/千克，腹腔注射），持续7天。随后，动物被暴露于不同的应激源，即在训练期间利用低强度（0.5毫安）或高强度（1.5毫安）足底电击进行条件性情绪应激，或进行固定应激。应激程序结束后，立即采集血样，用于放射免疫测定血浆皮质酮、催乳素和肾素浓度。重复接触可卡因会减弱应激诱导的皮质酮和催乳素分泌升高，并减弱低强度条件性情绪应激的一些行为效应。当暴露于高强度条件性情绪应激时，可卡因不会改变应激的内分泌或行为效应。最后，重复接触可卡因改变了固定应激诱导的肾素分泌升高；低剂量的可卡因（1或5毫克/千克）会减弱，而高剂量（10毫克/千克）会增强肾素对固定应激的反应。因此，重复接触可卡因对应激的内分泌和行为反应的影响似乎取决于应激源的类型和强度。与之前发现可卡因暴露后对血清素释放剂和激动剂的神经内分泌反应发生改变的研究相比，可卡因对应激的激素反应的改变不太一致。
