5-羟色胺（5-HT）1A 受体激动剂LY 228729对产前暴露于苯二氮䓬类药物的大鼠的运动及抗抑郁样作用

Locomotor and antidepressant-like effects of 5-HT(1A) agonist LY 228729 in prenatally benzodiazepine-exposed rats.

作者信息

Cannizzaro C, Cannizzaro E, Gagliano M, Mineo A

机构信息

Institute of Pharmacology, Faculty of Medicine, University of Palermo, Policlinico P. Giaccone, Italy.

出版信息

Eur Neuropsychopharmacol. 1998 Feb;8(1):27-32. doi: 10.1016/s0924-977x(97)00038-2.

DOI:10.1016/s0924-977x(97)00038-2

PMID:9452937

Abstract

Locomotor activity and antidepressant-like effect in the forced swim test (FST) of 5-HT(1A) agonist LY 228729 were investigated in adult rats prenatally exposed at doses of diazepam (DZ) and alprazolam (ALP) which induce persistent downregulation of GABA/ benzodiazepine (BZ) receptors. Prenatal exposure to ALP and DZ did not modify the efficacy of subchronic LY 228729 to decrease immobility time in the FST. Prenatal DZ and ALP potentiated the facilitatory effect of subchronic LY 228729 on locomotor activity; prenatal DZ was more effective than prenatal ALP. Moreover, prenatal DZ increased stereotypic movements induced by LY 228729. These data suggest that the persistent downregulation of GABA/BZ receptors, induced by prenatal BZs, does not play a role in the anti-immobility effect in the FST of 5-HT(1A) agonist LY 228729 while it can increase locomotor activity and stereotypic movements. Moreover, this study indicates that increases in locomotor activity do not seem to influence the anti-immobility effect in the FST of LY 228729 in rats.

摘要

研究了5-羟色胺（5-HT）1A激动剂LY 228729在成年大鼠强迫游泳试验（FST）中的运动活性和抗抑郁样作用，这些成年大鼠在产前暴露于可诱导γ-氨基丁酸/苯二氮卓（GABA/BZ）受体持续下调的地西泮（DZ）和阿普唑仑（ALP）剂量下。产前暴露于ALP和DZ并未改变亚慢性LY 228729降低FST中不动时间的效果。产前DZ和ALP增强了亚慢性LY 228729对运动活性的促进作用；产前DZ比产前ALP更有效。此外，产前DZ增加了LY 228729诱导的刻板运动。这些数据表明，产前苯二氮卓类药物诱导的GABA/BZ受体持续下调在5-HT 1A激动剂LY 228729的FST抗不动作用中不起作用，而它可增加运动活性和刻板运动。此外，本研究表明运动活性的增加似乎并不影响LY 228729在大鼠FST中的抗不动作用。