REDUCTION OF PREDATOR ODOR-INDUCED ANXIETY IN MICE BY THE NEUROSTEROID 3-ALPHA-HYDROXY-4-PREGNEN-20-ONE (3-ALPHA-HP)

被引:37
作者
KAVALIERS, M
WIEBE, JP
GALEA, LAM
机构
[1] UNIV WESTERN ONTARIO, NEUROSCI PROGRAM, LONDON N6A 5C1, ON, CANADA
[2] UNIV WESTERN ONTARIO, DEPT ZOOL, HORMONAL REGULATORY MECHANISMS LAB, LONDON N6A 5C1, ON, CANADA
关键词
ANXIETY; ANXIOLYTIC; ODOR PREFERENCE; PREDATOR ODOR; NEUROSTEROID; 3-ALPHA-HYDROXY-4-PREGNEN-20-ONE (3-ALPHA-HP); GAMMA-AMINOBUTYRIC ACID; GABA RECEPTOR;
D O I
10.1016/0006-8993(94)91667-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The effects of the centrally produced allylic neurosteroid, 3 alpha-hydroxy-4-pregnen-20-one (3 alpha HP), on the responses of male mice to an aversive, anxiety-inducing, predator (cat) odor were examined in an odor preference test. Control untreated mice displayed an anxiogenic response to the cat odor, spending a minimal amount of time in a Y-maze in the vicinity of the cat odor. Intracerebroventricular (i.c.v.) administrations of 3 alpha HP had an anxiolytic action, resulting in significant dose-related (0.01-1.0 mu g) increases in the amount of time spent in the proximity of the cat odor. These anxiolytic effects of 3 alpha HP were stereospecific, with the stereoisomer, 3 beta-hydroxy-4-pregnen-20-one (3 beta HP) having no significant effects on odor preferences. The analgesic, morphine, also had no significant effects on the response to cat odor indicating that the anxiolytic actions of 3 alpha HP were unlikely to be related to any analgesic effects. The effects of 3 alpha HP were significantly reduced by peripheral administrations of the GABA(A) antagonists, bicuculline and picrotoxin, but were unaffected by either the benzodiazepine antagonist, Ro 15-1788, or the opiate antagonist, naloxone. These results indicate that the allylic neurosteroid 3 alpha HP has anxiolytic actions involving interactions with the GABA(A) receptor.
引用
收藏
页码:325 / 329
页数:5
相关论文
共 28 条
[1]   ANXIOLYTIC EFFECT OF PROGESTERONE IS ASSOCIATED WITH INCREASES IN CORTICAL ALLOPREGNANOLONE AND GABA(A) RECEPTOR FUNCTION [J].
BITRAN, D ;
PURDY, RH ;
KELLOGG, CK .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1993, 45 (02) :423-428
[2]   ANXIOLYTIC EFFECTS OF 3A-HYDROXY-5A[BETA]-PREGNAN-20-ONE - ENDOGENOUS METABOLITES OF PROGESTERONE THAT ARE ACTIVE AT THE GABA-A RECEPTOR [J].
BITRAN, D ;
HILVERS, RJ ;
KELLOGG, CK .
BRAIN RESEARCH, 1991, 561 (01) :157-161
[3]  
BLANCHARD DC, 1991, PHARMACOL BIOCHEM BE, V40, P819
[4]   THE CHARACTERIZATION AND MODELING OF ANTIPREDATOR DEFENSIVE BEHAVIOR [J].
BLANCHARD, RJ ;
BLANCHARD, DC ;
RODGERS, J ;
WEISS, SM .
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, 1990, 14 (04) :463-472
[5]  
BLANCHARD RJ, 1989, NATO ADV SCI I D-BEH, V48, P114
[6]  
BRITTON KT, 1991, J PHARMACOL EXP THER, V258, P124
[7]  
COOPERSMITH CB, 1992, ETHOLOGY, V90, P1, DOI 10.1111/j.1439-0310.1992.tb00815.x
[8]   ANXIOLYTIC ACTIVITY OF AN ENDOGENOUS ADRENAL-STEROID [J].
CRAWLEY, JN ;
GLOWA, JR ;
MAJEWSKA, MD ;
PAUL, SM .
BRAIN RESEARCH, 1986, 398 (02) :382-385
[9]   SUPPRESSION OF FOLLICLE-STIMULATING-HORMONE BY THE GONADAL- AND NEUROSTEROID 3-ALPHA-HYDROXY-4-PREGNEN-20-ONE INVOLVES ACTIONS AT THE LEVEL OF THE GONADOTROPE MEMBRANE/CALCIUM CHANNEL [J].
DHANVANTARI, S ;
WIEBE, JP .
ENDOCRINOLOGY, 1994, 134 (01) :371-376
[10]  
FILE SE, 1991, INT CONGR SER, V941, P159