title: Elevations of FosB in the nucleus accumbens during forced cocaine abstinence correlate with divergent changes in reward function.
abstract: Dysregulation of hedonic processing, in which seeking of drug reward becomes more desirable than seeking natural rewards, like food, sex, and novelty, is a consequence of chronic drug exposure and potentially leads to escalating drug usage and addiction. Here, we investigated the effects of chronic cocaine treatment (10 days of escalating doses of cocaine, 10-30 mg/kg) and multiple forced abstinence periods (2, 3 or 5 weeks) on the acute rewarding properties of either cocaine (10 mg/kg) or novel-objects using the conditioned place preference procedure. Following all cocaine withdrawal periods, cocaine preference was significantly elevated while novel object preference was abolished compared with saline-treated rats. At the earliest withdrawal period, these behavioral changes were accompanied by elevations in FosB-like immunoreactive staining in the basolateral amygdala (BLA) and nucleus accumbens shell (NAc-Sh) and core (NAc-C). FosB staining in all three brain areas correlated positively with cocaine preference, but negatively with novelty preference. After 5 weeks of withdrawal, FosB staining was only elevated in the NAc-Sh and again correlated positively with elevated cocaine preference but negatively with decreased novelty preference. These data indicate that alterations in the expression of FosB-like transcription factors in the NAc can predict the dysregulation of hedonic processing that occurs during protracted withdrawal from cocaine.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: G C
authors.initials: GC
authors.lastname: Harris
authors.forename: M
authors.initials: M
authors.lastname: Hummel
authors.forename: M
authors.initials: M
authors.lastname: Wimmer
authors.forename: S D
authors.initials: SD
authors.lastname: Mague
authors.forename: G
authors.initials: G
authors.lastname: Aston-Jones
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D003042:Cocaine / Q000009:adverse effects*; D003216:Conditioning, Operant; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D013599:Systole
chemical_list: D018765:Dopamine Uptake Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D003042:Cocaine