title: Sex differences in behavioral and PKA cascade responses to repeated cocaine administration.
abstract: Previous studies have shown sex different patterns in behavioral responses to cocaine. Here, we used between-subject experiment design to study whether sex differences exist in the development of behavioral sensitization and tolerance to repeated cocaine, as well as the role of protein kinase A (PKA) signaling cascade in this process. Ambulatory and rearing responses were recorded in male and female rats after 1 to 14 days of administration of saline or cocaine (15 mg/kg; ip). Correspondent PKA-associated signaling in the nucleus accumbens (NAc) and caudate-putamen (CPu) was measured at each time point. Our results showed that females exhibited higher cocaine-induced behavioral responses and developed behavioral sensitization and tolerance faster than males. Whereas females developed behavioral sensitization to cocaine after 2 days and tolerance after 14 days, male rats developed sensitization after 5 days. In addition, cocaine induced a sexual dimorphic pattern in the progression of neuronal adaptations on the PKA cascade signaling in region (NAc vs. CPu) and time (days of cocaine administration)-dependent manners. In general, more PKA signaling cascade changes were found in the NAc of males on day 5 and in the CPu of females with repeated cocaine injection. In addition, in females, behavioral activities positively correlated with FosB levels in the NAc and CPu and negatively correlated with Cdk5 and p35 in the CPu, while no correlation was observed in males. Our studies suggest that repeated cocaine administration induced different patterns of behavioral and molecular responses in the PKA cascade in male and female rats.
authors.affiliation: Department of Biological Sciences, Hunter College of the City University of New York, New York, NY, 10065, USA.|Department of Biology PhD Program, Graduate School and University Center of the City University of New York, New York, NY, 10016, USA.|Department of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, SC, 29208, USA.
authors.forename: Luyi
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, SC, 29208, USA.|Department of Psychology, Hunter College of the City University of New York, New York, NY, 10065, USA.|Department of Biopsychology and Behavioral Neuroscience PhD Subprogram, Graduate School and University Center of the City University of New York, New York, NY, 10016, USA.
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Sun
authors.affiliation: Department of Psychology, Hunter College of the City University of New York, New York, NY, 10065, USA.|Department of Biopsychology and Behavioral Neuroscience PhD Subprogram, Graduate School and University Center of the City University of New York, New York, NY, 10016, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Weierstall
authors.affiliation: Department of Psychology, Hunter College of the City University of New York, New York, NY, 10065, USA.|Department of Biopsychology and Behavioral Neuroscience PhD Subprogram, Graduate School and University Center of the City University of New York, New York, NY, 10016, USA.
authors.forename: Ana Christina
authors.initials: AC
authors.lastname: Minerly
authors.affiliation: Department of Psychology, Hunter College of the City University of New York, New York, NY, 10065, USA.|Department of Biopsychology and Behavioral Neuroscience PhD Subprogram, Graduate School and University Center of the City University of New York, New York, NY, 10016, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Weiner
authors.affiliation: Department of Psychology, Hunter College of the City University of New York, New York, NY, 10065, USA.|Department of Biopsychology and Behavioral Neuroscience PhD Subprogram, Graduate School and University Center of the City University of New York, New York, NY, 10016, USA.
authors.forename: Shirzad
authors.initials: S
authors.lastname: Jenab
authors.affiliation: Department of Biology PhD Program, Graduate School and University Center of the City University of New York, New York, NY, 10016, USA. vanya.quinones@hunter.cuny.edu.|Department of Psychology, Hunter College of the City University of New York, New York, NY, 10065, USA. vanya.quinones@hunter.cuny.edu.|Department of Biopsychology and Behavioral Neuroscience PhD Subprogram, Graduate School and University Center of the City University of New York, New York, NY, 10016, USA. vanya.quinones@hunter.cuny.edu.
authors.forename: Vanya
authors.initials: V
authors.lastname: Quinones-Jenab
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002421:Caudate Nucleus / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D051360:Cyclin-Dependent Kinase 5 / Q000187:drug effects / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004361:Drug Tolerance; D005260:Female; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010770:Phosphotransferases / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D011699:Putamen / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C492235:Cdk5r1 protein, rat; D018765:Dopamine Uptake Inhibitors; C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos; D010770:Phosphotransferases; D051360:Cyclin-Dependent Kinase 5; D017868:Cyclic AMP-Dependent Protein Kinases; C495907:Cdk5 protein, rat; D003042:Cocaine
keywords: Addiction; Cocaine; Female; FosB; PKA; Sex differences