title: Effect of ΔFosB overexpression on opioid and cannabinoid receptor-mediated signaling in the nucleus accumbens.
abstract: The stable transcription factor ΔFosB is induced in the nucleus accumbens (NAc) by chronic exposure to several drugs of abuse, and transgenic expression of ΔFosB in the striatum enhances the rewarding properties of morphine and cocaine. However, the mechanistic basis for these observations is incompletely understood. We used a bitransgenic mouse model with inducible expression of ΔFosB in dopamine D(1) receptor/dynorphin-containing striatal neurons to determine the effect of ΔFosB expression on opioid and cannabinoid receptor signaling in the NAc. Results showed that mu opioid-mediated G-protein activity and inhibition of adenylyl cyclase were enhanced in the NAc of mice that expressed ΔFosB. Similarly, kappa opioid inhibition of adenylyl cyclase was enhanced in the ΔFosB expressing mice. In contrast, cannabinoid receptor-mediated signaling did not differ between mice overexpressing ΔFosB and control mice. These findings suggest that opioid and cannabinoid receptor signaling are differentially modulated by expression of ΔFosB, and indicate that ΔFosB expression might produce some of its effects via enhanced mu and kappa opioid receptor signaling in the NAc.
authors: Department of Pharmacology and Toxicology and Institute for Drug and Alcohol Studies, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
authors: Laura J
authors: LJ
authors: Sim-Selley
authors: Michael P
authors: MP
authors: Cassidy
authors: Antonino
authors: A
authors: Sparta
authors: Venetia
authors: V
authors: Zachariou
authors: Eric J
authors: EJ
authors: Nestler
authors: Dana E
authors: DE
authors: Selley
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000227:Adenine Nucleotides / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000493:pharmacokinetics; D000262:Adenylyl Cyclases / Q000378:metabolism; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000235:genetics; D010759:Phosphorus Isotopes / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013460:Sulfur Isotopes / Q000493:pharmacokinetics
chemical_list: D000227:Adenine Nucleotides; D000701:Analgesics, Opioid; D048588:Benzoxazines; D002121:Calcium Channel Blockers; C483819:Fosb protein, mouse; D009025:Morpholines; D009281:Naphthalenes; D010759:Phosphorus Isotopes; D016760:Proto-Oncogene Proteins c-fos; D043884:Receptor, Cannabinoid, CB1; D013460:Sulfur Isotopes; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000255:Adenosine Triphosphate; D010751:Phosphopyruvate Hydratase; D000262:Adenylyl Cyclases