Cocaine pre-exposure enhances CRF-induced expression of c-fos mRNA in the central nucleus of the amygdala: an effect that parallels the effects of cocaine pre-exposure on CRF-induced locomotor activity.
There is evidence that cocaine pre-exposure produces changes in the responsivity of central corticotropin-releasing factor (CRF) systems and that these systems mediate some of the drug-related behavioural effects of acute stressors. The present experiment was conducted to assess the effects of repeated cocaine exposure on CRF-induced neuronal activation within two regions of the extended amygdala, the central nucleus of the amygdala (CeA) and lateral bed nucleus of the stria terminalis (BNST). In addition, CRF-induced neuronal activation was compared with CRF-induced locomotor activity. Rats were injected for 7 days with cocaine (days 1 and 7 in test chambers; days 2-6 in homecages) or saline. After 10 drug-free days, locomotor responsiveness to intracerebroventricular (i.c.v.) injections of CRF and Vehicle was assessed over 2-h test periods. Twenty-four to 48 h following testing for locomotor activity, animals were injected with either CRF or Vehicle, 30 min before being sacrificed. Subsequently, the brains were processed by in situ hybridization for c-fos mRNA, a widely used marker of neuronal activation, in the CeA and BNST. In CeA, i.c.v. CRF enhanced the expression of c-fos mRNA in cocaine, but not saline, pre-exposed animals; in the same animals, i.c.v. CRF resulted in enhanced locomotor activity in cocaine, but not saline, pre-exposed animals. The results demonstrate that repeated exposure to cocaine changes the neuronal response to CRF in the CeA; furthermore, they suggest that these changes in the CeA could potentially be of functional significance in the effects of repeated cocaine exposure on CRF-induced locomotor activity.
Erb
Suzanne
S
Centre for the Neurobiology of Stress, Departments of Life Science and Psychology, University of Toronto at Scarborough, 1265 Military Trail, Toronto, Ont., Canada M1C 1A4. erb@utsc.utoronto.ca
Funk
Douglas
D
Lê
Anh Dzung
AD
D000679:Amygdala / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal; D003042:Cocaine / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D018765:Dopamine Uptake Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D003346:Corticotropin-Releasing Hormone; D003042:Cocaine