Bitran D, Shiekh M, Dowd J A, Dugan M M, Renda P
Department of Psychology, College of the Holy Cross, Worcester, MA 01610, USA.
Pharmacol Biochem Behav. 1998 Aug;60(4):879-87. doi: 10.1016/s0091-3057(98)00071-9.
The effects of RU 28318, a mineralocorticoid receptor antagonist (A-MR), and RU 38486, a glucocorticoid receptor antagonist (A-GR) on behavior in three animal models of anxiety were assessed after microinjection into the dorsal hippocampus. Significant anxiolytic effects were observed after intrahippocampal injection of 0.5, and 1 ng of A-MR in thigmotaxic behavior in the open field, in the elevated plus-maze, and in the defensive burying test. Lower (0.2 ng) or higher (5 ng) doses of A-MR were ineffective, as were comparable injections of A-GR or microinjections of combined A-MR and A-GR. The anxiolytic effect of intrahippocampal A-MR administration observed in the elevated plus-maze and in the open field was not observed in adrenalectomized animals or in animals pretreated with a systemic injection of dexamethasone (80 mg/kg). Intrahippocampal injection of 1 ng of A-MR or A-GR prevented the return to basal corticosterone levels observed 90 min after restraint stress. This effect was reversed in dexamethasone-pretreated animals. The results are discussed in light of recent findings implicating the role of the MR in the hippocampus in adaptive behavioral responses to an aversive or threatening environment, and further implicate the permissive role of corticosterone in A-MR-induced behavioral responses.
将盐皮质激素受体拮抗剂RU 28318（A-MR）和糖皮质激素受体拮抗剂RU 38486（A-GR）微量注射到背侧海马后，评估了它们对三种焦虑动物模型行为的影响。在旷场、高架十字迷宫和防御性埋埋实验中，海马内注射0.5 ng和1 ng的A-MR后，在趋触性（thigmotaxic）行为中观察到显著的抗焦虑作用。较低剂量（0.2 ng）或较高剂量（5 ng）的A-MR无效，同样剂量的A-GR注射或A-MR与A-GR联合微量注射也无效。在高架十字迷宫和旷场中观察到的海马内注射A-MR的抗焦虑作用，在肾上腺切除的动物或全身注射地塞米松（80 mg/kg）预处理的动物中未观察到。海马内注射1 ng的A-MR或A-GR可阻止在束缚应激90分钟后观察到的皮质酮水平恢复到基础水平。在地塞米松预处理的动物中，这种作用被逆转。根据最近的研究结果讨论了这些结果，这些研究结果表明海马中的盐皮质激素受体在对厌恶或威胁环境的适应性行为反应中的作用，并进一步表明皮质酮在A-MR诱导的行为反应中的允许作用。
