Papolos D F, Edwards E, Marmur R, Lachman H M, Henn F A
Department of Psychiatry, Albert Einstein College of Medicine, Bronx, NY 10461.
Brain Res. 1993 Jul 2;615(2):304-9. doi: 10.1016/0006-8993(93)90042-l.
Learned helplessness (LH) is induced by exposure to an inescapable or uncontrollable stressor which results in an inability to escape or avoid the same stressor when subsequently presented in a different context. In order to understand which central mechanisms may influence the expression of the learned helpless phenotype, we have pursued an experimental approach that seeks to elucidate the behavioral effects of glucocorticoid (GC) hormones in this animal model of depression. We have previously shown that the induction of LH behavior is enhanced by adrenalectomy, an effect that is reversed by corticosterone. In this study, our aim was to attempt to locate CNS sites responsible for the observed effects of glucocorticoids on learned helpless behavior by introducing the type II GC receptor antagonist, RU 38486 to discrete brain regions. We did not observe a significant effect in LH with acute systemic, acute dentate gyrus or intracerebroventricular injection of RU 38486 in contrast to previous studies using the Porsolt swim test, another animal model of depression. However, we were able to observe a significant change upon chronic administration to the dentate gyrus. These findings suggest that glucocorticoids exert a long-term influence on stress-induced behavior, presumably by affecting glucocorticoid responsive genes in the dentate gyrus.
习得性无助（LH）是由暴露于不可逃避或无法控制的应激源所诱发的，这会导致在随后不同情境中再次出现相同应激源时，个体无法逃脱或避开它。为了了解哪些中枢机制可能影响习得性无助表型的表达，我们采用了一种实验方法，旨在阐明糖皮质激素（GC）在这种抑郁症动物模型中的行为效应。我们之前已经表明，肾上腺切除术会增强LH行为的诱导，而皮质酮可逆转这一效应。在本研究中，我们的目的是通过将II型GC受体拮抗剂RU 38486引入离散的脑区，试图确定对糖皮质激素对习得性无助行为的观察效应负责的中枢神经系统部位。与之前使用另一种抑郁症动物模型——波索尔特游泳试验的研究不同，我们在急性全身、急性齿状回或脑室内注射RU 38486时，未观察到对LH有显著影响。然而，在对齿状回进行慢性给药后，我们能够观察到显著变化。这些发现表明，糖皮质激素可能通过影响齿状回中的糖皮质激素反应基因，对应激诱导的行为产生长期影响。
