title: Differential effects of the MEK inhibitor SL327 on the acquisition and expression of ethanol-elicited conditioned place preference and aversion in mice.
abstract: The involvement of mitogen-activating extracellular kinase (MEK) in place conditioning may vary depending on the motivational sign (positive or negative) and nature (pharmacological or nociceptive) of the unconditioned stimulus (US) and on the phase (acquisition or expression) of the learning process. This study investigated the role of MEK on the acquisition and expression of ethanol-elicited (given 2 g/kg) backward (preference, CPP) and forward (aversion, CPA) place conditioning. The MEK inhibitor SL327 (50 mg/kg for CPP, and 50 and 100 mg/kg for CPA) was administered to CD-1 mice 60 minutes before an ethanol dose (acquisition) or 60 minutes before the post-conditioning tests (expression). Ethanol significantly elicited CPP and CPA; SL327 (50 mg/kg) significantly blocked the acquisition of ethanol-elicited CPP, but not that of CPA. Moreover, SL327 (50 and 100 mg/kg) significantly reduced the expression of ethanol-elicited CPP, but not that of CPA. Finally, SL327 also prevented ethanol-elicited (given 2 g/kg) increases of phosphorylated extracellular signal regulated kinase (pERK)-positive neurons in the nucleus accumbens and other nuclei of the extended amygdala. Overall, these results confirmed the differential involvement of MEK in the acquisition and expression of drug-elicited place conditioning and suggested its differential involvement in distinct behavioral outcomes, depending on the motivational sign of the (same) US and on the significance of the experimental phase of the learning process.
authors.affiliation: 1 Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Rosas
authors.affiliation: 1 Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Porru
authors.affiliation: 1 Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Longoni
authors.affiliation: 1 Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Liliana
authors.initials: L
authors.lastname: Spina
authors.affiliation: 2 Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy.
authors.forename: Alessandra T
authors.initials: AT
authors.lastname: Peana
authors.affiliation: 3 Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.|4 Centre of Excellence in the Neurobiology of Addiction, University of Cagliari, Cagliari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Collu
authors.affiliation: 1 Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.|4 Centre of Excellence in the Neurobiology of Addiction, University of Cagliari, Cagliari, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Acquas
mesh_terms: D000607:Aminoacetonitrile / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000187:drug effects*; D000431:Ethanol / Q000009:adverse effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D007858:Learning / Q000187:drug effects; D008297:Male; D051379:Mice; D009042:Motivation / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects; D012201:Reward
chemical_list: C424127:SL 327; D000607:Aminoacetonitrile; D000431:Ethanol; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: CD-1 mice; Conditioned place aversion; SL327; conditioned place preference; ethanol; extracellular signal-regulated kinase; learning; mitogen-activating extracellular kinase; reinforcement