title: ΔFosB in the nucleus accumbens is critical for reinforcing effects of sexual reward.
abstract: Sexual behavior in male rats is rewarding and reinforcing. However, little is known about the specific cellular and molecular mechanisms mediating sexual reward or the reinforcing effects of reward on subsequent expression of sexual behavior. This study tests the hypothesis that ΔFosB, the stably expressed truncated form of FosB, plays a critical role in the reinforcement of sexual behavior and experience-induced facilitation of sexual motivation and performance. Sexual experience was shown to cause ΔFosB accumulation in several limbic brain regions including the nucleus accumbens (NAc), medial prefrontal cortex, ventral tegmental area and caudate putamen but not the medial preoptic nucleus. Next, the induction of c-Fos, a downstream (repressed) target of ΔFosB, was measured in sexually experienced and naïve animals. The number of mating-induced c-Fos-immunoreactive cells was significantly decreased in sexually experienced animals compared with sexually naïve controls. Finally, ΔFosB levels and its activity in the NAc were manipulated using viral-mediated gene transfer to study its potential role in mediating sexual experience and experience-induced facilitation of sexual performance. Animals with ΔFosB overexpression displayed enhanced facilitation of sexual performance with sexual experience relative to controls. In contrast, the expression of ΔJunD, a dominant negative binding partner of ΔFosB, attenuated sexual experience-induced facilitation of sexual performance and stunted long-term maintenance of facilitation compared to green fluorescence protein and ΔFosB overexpressing groups. Together, these findings support a critical role for ΔFosB expression in the NAc for the reinforcing effects of sexual behavior and sexual experience-induced facilitation of sexual performance.
authors.affiliation: Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: K K
authors.initials: KK
authors.lastname: Pitchers
authors.forename: K S
authors.initials: KS
authors.lastname: Frohmader
authors.forename: V
authors.initials: V
authors.lastname: Vialou
authors.forename: E
authors.initials: E
authors.lastname: Mouzon
authors.forename: E J
authors.initials: EJ
authors.lastname: Nestler
authors.forename: M N
authors.initials: MN
authors.lastname: Lehman
authors.forename: L M
authors.initials: LM
authors.lastname: Coolen
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000235:genetics / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D005822:Genetic Vectors; D007124:Immunoenzyme Techniques; D008297:Male; D009042:Motivation / Q000235:genetics / Q000502:physiology; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000378:metabolism* / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012201:Reward; D012726:Sexual Behavior, Animal / Q000502:physiology*
chemical_list: C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos