S. Malkani et Jb. Rosen, Differential expression of EGR-1 mRNA in the amygdala following diazepam in contextual fear conditioning, BRAIN RES, 860(1-2), 2000, pp. 53-63
The amygdaloid complex is thought to be a major site of action of anxiolyti
c benzodiazepine agonists. To investigate whether activity in the amygdaloi
d complex is altered with anxiolytic effects of diazepam, mRNA expression o
f the immediate-early gene EGR-1 was examined in the amygdala following blo
ckade of fear conditioning by diazepam. It was previously shown that mRNA e
xpression of EGR-1 (also called, NGFI-A, Zif 268, Krox 24) increases in the
lateral nucleus of the amygdala (LA) shortly following contextual fear con
ditioning. It was therefore hypothesized that diazepam would block both con
textual fear and the concomitant increase in EGR-1 mRNA expression in the L
A induced by fear conditioning. Rats administered systemic diazepam before
fear conditioning displayed both anxiolytic effects during the post-shock p
eriod and amnesic effects during a retention test 24 h later. Diazepam bloc
ked the fear-conditioning-induced increase in EGR-1 expression in the LA. I
n addition, diazepam significantly increased EGR-1 mRNA expression in the c
entral nucleus of the amygdala (CeA) in a dose-dependent manner. The result
s reveal differential regulation of EGR-1 by diazepam in the central and la
teral nuclei of the amygdala suggesting that these two amygdala nuclei act
in a reciprocal manner during the anxiolytic and amnesic action of the benz
odiazepine agonist. (C) 2000 Elsevier Science B.V. All rights reserved.