Increased CRH mRNA levels in the rat amygdala during short-term withdrawal from chronic 'binge' cocaine.
There is evidence that suggests that increased corticotropin-releasing hormone (CRH) release in the central nucleus of the amygdala underlies the anxiogenic and stress-like consequences of withdrawal that are common in phenomenology to all drugs of abuse. The present studies were undertaken to determine levels of CRH mRNA in the amygdala, and also in the hypothalamus, frontal cortex and brainstem after short-term (2 days) and intermediate-term (10 days) cocaine withdrawal (with continued saline injections) from chronic (14 days) 'binge' pattern cocaine administration (3 x 15 mg/kg per day at hourly intervals). Confirming our recent finding of an activation of stress responsive hypothalamic-pituitary-adrenal activity during early cocaine withdrawal, there was a significant elevation of plasma corticosterone level after 2-day cocaine withdrawal. There was also a significant elevation of CRH mRNA levels in the amygdala, but not in the hypothalamus, frontal cortex or brainstem after 2-day cocaine withdrawal. A negative correlation between amygdalar CRH mRNA and plasma corticosterone levels was found in the 2-day cocaine withdrawn rats but not in control rats, suggesting that CRH neurons in the amygdala may be differentially responsive to glucocorticoids after chronic cocaine exposure and withdrawal. There were no changes in either plasma corticosterone or amygdalar CRH mRNA levels after 10-day cocaine withdrawal. Our findings of an increase in amygdalar CRH gene expression during early cocaine withdrawal support a potentially important role for amygdalar CRH activity in the anxiogenic and aversive consequences of withdrawal from cocaine during a time when humans are most subject to relapse.
Zhou
Yan
Y
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. yan.zhou@rockefeller.edu
Spangler
Rudolph
R
Ho
Ann
A
Kreek
Mary Jeanne
MJ
D000679:Amygdala / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology; D002908:Chronic Disease; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004745:Enkephalins / Q000235:genetics; D005625:Frontal Lobe / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D018765:Dopamine Uptake Inhibitors; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D003346:Corticotropin-Releasing Hormone; C033660:preproenkephalin; D003042:Cocaine; D003345:Corticosterone