Suppression of c-fos induction in the nucleus accumbens prevents acquisition but not expression of morphine-conditioned place preference.
The c-fos immediate-early gene is induced by morphine and other drugs of abuse in the nucleus accumbens (NAc), a mesolimbic region implicated in drug abuse and reward. This study examined the role of c-fos in the acquisition and expression of the conditioned place paradigm (CPP) in the rat by suppressing Fos protein expression with c-fos antisense oligodeoxynucleotides (ODNs). CPP was completely prevented by c-fos antisense ODN infused bilaterally into the NAc prior to each systemic morphine injection, whereas sense and missense NAc injections had no effect on CPP. NAc administration of c-fos antisense ODN after the last systemic morphine conditioning session did not affect the expression of morphine-CPP. These results suggest that c-fos expression in NAc is necessary for the acquisition but not expression of morphine-CPP, and they have important implications for understanding conditioned behaviours and drug craving and addiction.
Tolliver
B K
BK
Department of Neurology, University of Cincinnati, Vontz Center for Molecular Studies Rm 2327, 3125 Eden Ave, University of Cincinnati, Cincinnati, OH 45267-0536, USA.
Sganga
M W
MW
Sharp
F R
FR
D000818:Animals; D016375:Antisense Elements (Genetics) / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000503:physiopathology; D009294:Narcotics / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016375:Antisense Elements (Genetics); D009294:Narcotics; D016760:Proto-Oncogene Proteins c-fos; D009020:Morphine