Marinelli M, Rougé-Pont F, Deroche V, Barrot M, De Jésus-Oliveira C, Le Moal M, Piazza P V
Psychobiologie des Comportements Adaptatifs, INSERM U 259, Université de Bordeaux II, France.
J Pharmacol Exp Ther. 1997 Jun;281(3):1392-400.
In this study, we explored the influence of corticosterone, the major glucocorticoid in the rat, on the locomotor response to cocaine. In particular, in a first series of experiments, we determined the effects of suppressing endogenous glucocorticoids by adrenalectomy on a full dose-response curve of cocaine-induced locomotion and the influence, on this behavioral response, of different corticosterone concentrations, by implanting different corticosterone pellets in adrenalectomized rats. Adrenalectomy decreased the locomotor response to cocaine, inducing a vertical shift in the dose-response curve, and corticosterone dose-dependently reversed the decrease induced by adrenalectomy. The effects of adrenalectomy were fully replicated by the acute central infusion of corticosteroid receptor antagonists, and the action of glucocorticoids did not seem to depend on nonspecific effects such as a general alteration of motor responses or drug metabolism. Thus, neither adrenalectomy, corticosterone receptor antagonists nor corticosterone replacement modified saline-induced locomotion and the administration of corticosterone did not increase locomotion. Furthermore, adrenalectomy slightly increased brain concentrations of cocaine, an effect that cannot account for the decrease in drug-induced locomotion it induced. In a second series of experiments, we tested whether corticosterone levels at the time of adrenalectomy could influence the outcome of this surgical procedure on the locomotor response to cocaine. We thus adrenalectomized rats under different conditions resulting in different levels of the hormone. Corticosterone levels at the moment of adrenalectomy had dose-dependent long-term facilitatory effects on the response to the drug. These findings underline a facilitatory role of glucocorticoids in the behavioral effects of psychostimulant drugs.
在本研究中，我们探讨了大鼠体内主要的糖皮质激素皮质酮对可卡因所致运动反应的影响。具体而言，在第一组实验中，我们通过肾上腺切除术抑制内源性糖皮质激素，测定其对可卡因诱导运动的全剂量反应曲线的影响，并通过给肾上腺切除的大鼠植入不同剂量的皮质酮微丸，研究不同皮质酮浓度对这种行为反应的影响。肾上腺切除术降低了对可卡因的运动反应，导致剂量反应曲线发生垂直位移，而皮质酮呈剂量依赖性地逆转了肾上腺切除术所致的降低。肾上腺切除术的效果可通过急性中枢注射糖皮质激素受体拮抗剂完全重现，且糖皮质激素的作用似乎并不依赖于诸如运动反应或药物代谢的一般改变等非特异性效应。因此，肾上腺切除术、皮质酮受体拮抗剂或皮质酮替代均未改变生理盐水诱导的运动，且给予皮质酮也未增加运动。此外，肾上腺切除术略微增加了脑中可卡因的浓度，这一效应无法解释其所致药物诱导运动的降低。在第二组实验中，我们测试了肾上腺切除时的皮质酮水平是否会影响该手术对可卡因运动反应的结果。因此，我们在不同条件下对大鼠进行肾上腺切除术，导致激素水平不同。肾上腺切除时的皮质酮水平对药物反应具有剂量依赖性的长期促进作用。这些发现强调了糖皮质激素在精神兴奋药物行为效应中的促进作用。
