Goeders N E, Guerin G F
Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport 71130-3932, USA.
Neuroendocrinology. 1996 Nov;64(5):337-48. doi: 10.1159/000127137.
The role of corticosterone in cocaine reinforcement was investigated in rats exposed to either response-contingent electric footshock, noncontingent shock or no shock prior to the initiation of testing for intravenous cocaine self-administration. Although rats from the two shock groups were consistently more sensitive to cocaine, plasma corticosterone was always significantly higher in all rats that subsequently self-administered low doses of cocaine compared to the rats that did not, regardless of the treatment condition. In fact, plasma corticosterone was always greater than approximately 150 ng/ml for rats that self-administered low doses of cocaine, suggesting that this stress hormone must be increased above a critical threshold for stable low-dose cocaine self-administration to subsequently occur. Plasma corticosterone was also measured following exposure to cocaine and was significantly elevated in rats from all three treatment groups during cocaine self-administration, provided that doses of cocaine that would maintain responding were tested. When the dose would not maintain self-administration, plasma corticosterone was markedly lower, suggesting that at higher concentrations, the cocaine injections alone were sufficient to increase plasma corticosterone above a critical threshold, even for rats which had low precocaine levels of the hormone. These data suggest a significant role for corticosterone in both the acquisition and maintenance of cocaine reinforcement in rats.
在开始静脉注射可卡因自我给药测试之前,对暴露于反应性电足部电击、非反应性电击或无电击的大鼠,研究了皮质酮在可卡因强化中的作用。尽管来自两个电击组的大鼠对可卡因始终更为敏感,但与未自我给药的大鼠相比,所有随后自我给药低剂量可卡因的大鼠,无论其治疗条件如何,血浆皮质酮水平始终显著更高。事实上,自我给药低剂量可卡因的大鼠血浆皮质酮水平始终大于约150 ng/ml,这表明这种应激激素必须升高到临界阈值以上,随后才会出现稳定的低剂量可卡因自我给药。在接触可卡因后也测量了血浆皮质酮,只要测试了能维持反应的可卡因剂量,在所有三个治疗组的大鼠可卡因自我给药期间,血浆皮质酮都显著升高。当剂量不能维持自我给药时,血浆皮质酮明显较低,这表明在较高浓度下,仅可卡因注射就足以使血浆皮质酮升高到临界阈值以上,即使对于可卡因给药前激素水平较低的大鼠也是如此。这些数据表明皮质酮在大鼠可卡因强化的获得和维持中都起着重要作用。