The effects of cocaine on CART expression in the rat nucleus accumbens: a possible role for corticosterone.
CART (Cocaine- and Amphetamine-Regulated Transcript) was initially described as an mRNA which had increased expression in the rat striatum following administration of acute cocaine or amphetamine but not saline. However, not all subsequent studies confirmed this. The present study aimed to repeat experiments with conflicting results and to reexamine and extend the original finding of acute regulation of nucleus accumbens CART mRNA by cocaine. Acute administration of cocaine failed to produce any change in levels of CART mRNA or peptide. Chronic administration of cocaine, as well as unilateral 6-hydroxydopamine lesions, also failed to alter CART mRNA levels in the accumbens. However, binge administration of cocaine, which also caused some seizures, did cause a significant increase in CART message. Given the involvement of corticosteroids with both stress and the effects of psychostimulants, we examined the possible effects of corticosteroids. We acutely administered ascending doses of corticosterone and found an increase in CART message. Similar effects were seen on CART peptides after acute corticosterone administration, and acute metyrapone administration was found to reduce CART peptide levels in the accumbens. This suggests that CART mRNA may be regulated by cocaine under certain conditions, such as binge administration, and this may at least partly involve corticosterone.
Emory University Department of Pharmacology, Atlanta, GA 30329, USA.
Richard G
RG
Hunter
Aleksandra
A
Vicentic
George
G
Rogge
Michael J
MJ
Kuhar
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003345:Corticosterone / Q000494:pharmacology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D017403:In Situ Hybridization; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D000963:Antimetabolites; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D003042:Cocaine; D003345:Corticosterone; D008797:Metyrapone