Differential expression of EGR-1 mRNA in the amygdala following diazepam in contextual fear conditioning.
The amygdaloid complex is thought to be a major site of action of anxiolytic benzodiazepine agonists. To investigate whether activity in the amygdaloid complex is altered with anxiolytic effects of diazepam, mRNA expression of the immediate-early gene EGR-1 was examined in the amygdala following blockade of fear conditioning by diazepam. It was previously shown that mRNA expression of EGR-1 (also called, NGFI-A, Zif 268, Krox 24) increases in the lateral nucleus of the amygdala (LA) shortly following contextual fear conditioning. It was therefore hypothesized that diazepam would block both contextual fear and the concomitant increase in EGR-1 mRNA expression in the LA induced by fear conditioning. Rats administered systemic diazepam before fear conditioning displayed both anxiolytic effects during the post-shock period and amnesic effects during a retention test 24 h later. Diazepam blocked the fear-conditioning-induced increase in EGR-1 expression in the LA. In addition, diazepam significantly increased EGR-1 mRNA expression in the central nucleus of the amygdala (CeA) in a dose-dependent manner. The results reveal differential regulation of EGR-1 by diazepam in the central and lateral nuclei of the amygdala suggesting that these two amygdala nuclei act in a reciprocal manner during the anxiolytic and amnesic action of the benzodiazepine agonist.
Malkani
S
S
Program in Neuroscience, Department of Psychology, University of Delaware, 220 Wolf Hall, Newark, DE, USA.
Rosen
J B
JB
D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003216:Conditioning, Operant; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D003975:Diazepam / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1; D004597:Electroshock; D005239:Fear; D058785:GABA-A Receptor Agonists; D005786:Gene Expression Regulation / Q000187:drug effects*; D017781:Genes, Immediate-Early; D007091:Image Processing, Computer-Assisted; D017874:Immediate-Early Proteins; D017403:In Situ Hybridization; D008297:Male; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
D014151:Anti-Anxiety Agents; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D058785:GABA-A Receptor Agonists; D017874:Immediate-Early Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D003975:Diazepam