Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6228027 | Biological Psychiatry | 2012 | 7 Pages |
BackgroundElevated expression of the transcription factor ÎFosB accompanies repeated exposure to drugs of abuse, particularly in brain areas associated with reward and motivation (e.g., nucleus accumbens). The persistent effects of ÎFosB on target genes might play an important role in the development and expression of behavioral adaptations that characterize addiction. This study examines how ÎFosB influences the responsiveness of the brain reward system to rewarding and aversive drugs.MethodsWe used the intracranial self-stimulation paradigm to assess the effects of cocaine in transgenic mice with inducible overexpression of ÎFosB in striatal regions (including nucleus accumbens and dorsal striatum). Mice implanted with lateral hypothalamic stimulating electrodes were trained with the “rate-frequency” procedure for intracranial self-stimulation to determine the frequency at which stimulation becomes rewarding (threshold).ResultsA dose-effect analysis of cocaine effects revealed that mice overexpressing ÎFosB show increased sensitivity to the rewarding (threshold-lowering) effects of the drug, compared with littermate control subjects. Interestingly, mice overexpressing ÎFosB were also less sensitive to the pro-depressive (threshold-elevating) effects of U50488, a kappa-opioid agonist known to induce dysphoria and stress-like effects in rodents.ConclusionsThese data suggest that induction of ÎFosB in striatal regions has two important behavioral consequences-increased sensitivity to drug reward, and reduced sensitivity to aversion-producing a complex phenotype that shows signs of vulnerability to addiction as well as resilience to stress.