title: Maladaptive Sexual Behavior Following Concurrent Methamphetamine and Sexual Experience in Male Rats is Associated with Altered Neural Activity in Frontal Cortex.
abstract: The use of psychostimulants is often associated with hypersexuality, and psychostimulant users have identified the effects of drug on sexual behavior as a reason for further use. It was previously demonstrated in male rats that methamphetamine (Meth), when administered concurrently with sexual behavior results in impairment of inhibition of sexual behavior in a conditioned sex aversion (CSA) paradigm where mating is paired with illness. This is indicative of maladaptive sex behavior following Meth and sex experience. The present study examined the neural pathways activated during inhibition of sexual behavior in male rats and the effects of concurrent Meth and sexual behavior on neural activity, using ERK phosphorylation (pERK). First, exposure to conditioned aversive stimuli in males trained to inhibit sexual behavior in the CSA paradigm increased pERK expression in medial prefrontal (mPFC), orbitofrontal cortex (OFC) and areas in striatum and amygdala. Second, effects of concurrent Meth and sex experience were tested in males that were exposed to four daily sessions of concurrent Meth (1 mg/kg) or saline and mating and subsequently exposed to CSA one week after last treatment. Meth and mating-treated males showed significant impairment of inhibition of mating, higher pERK expression under baseline conditions, and disrupted pERK induction by exposure to the conditioned aversive stimuli in mPFC and OFC. These alterations of pERK occurred in CaMKII-expressing neurons, suggesting changes in efferent projections of these areas. Altogether, these data show that concurrent Meth and mating experience causes maladapative sexual behavior that is associated with alterations in neural activation in mPFC and OFC.
authors.affiliation: Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, MS, USA.|Graduate Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Lindsey B
authors.initials: LB
authors.lastname: Kuiper
authors.affiliation: Department of Anatomy &Cell Biology, The University of Western Ontario, London, Ontario, Canada.|Department of Molecular &Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Karla S
authors.initials: KS
authors.lastname: Frohmader
authors.affiliation: Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, MS, USA.|Department of Anatomy &Cell Biology, The University of Western Ontario, London, Ontario, Canada.|Department of Molecular &Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Lique M
authors.identifier: http://orcid.org/0000-0003-2920-1116
authors.initials: LM
authors.lastname: Coolen
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007150:Immunohistochemistry; D008032:Limbic System / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D012726:Sexual Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D020018:Sexual Dysfunctions, Psychological / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048049:Extracellular Signal-Regulated MAP Kinases; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2