title: Inhibition of extracellular signal-regulated kinase (ERK) activity with SL327 does not prevent acquisition, expression, and extinction of ethanol-seeking behavior in mice.
abstract: Although extracellular signal-regulated kinase (ERK) activity is essential for the acquisition of a variety of associative learning tasks, its involvement in the acquisition and extinction of ethanol (EtOH)-induced conditioned place preference (CPP) remains unknown. Therefore, in these experiments we examined the effects of the ERK-kinase (MEK)-inhibitor SL327 on acquisition and expression of EtOH-CPP as well as the dose- and time-dependent effects of SL327 on CPP extinction. The parametric findings of Experiment 1 showed that three 30-min (but not 15- or 5-min) non-reinforced trials were required to completely extinguish EtOH-CPP in male, DBA/2J mice. In Experiments 2 and 3, SL327 (30 and 50mg/kg), administered 30 or 90min prior to extinction trials, was unable to impair EtOH-CPP extinction. Experiment 4 showed that SL327 (50mg/kg) had no effect on acquisition of EtOH-CPP or the development of EtOH-induced sensitization during conditioning. When administered prior to testing in Experiments 5 and 6, SL327 did not alter expression of EtOH-CPP but did reduce test activity. Importantly, SL327 significantly reduced pERK protein levels when assessed in the dorsal striatum and motor cortex (Experiment 7). Together, these data suggest that EtOH-related learning and EtOH reward in mice, as assessed with CPP, are not impaired by the systemically administered MEK-inhibitor SL327.
authors.affiliation: Dept. of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239-3098, USA. groblews@ohsu.edu
authors.forename: Peter A
authors.initials: PA
authors.lastname: Groblewski
authors.forename: Frederick H
authors.initials: FH
authors.lastname: Franken
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Cunningham
mesh_terms: D000607:Aminoacetonitrile / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D012054:Reinforcement, Psychology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; C424127:SL 327; D000607:Aminoacetonitrile; D000431:Ethanol; D048049:Extracellular Signal-Regulated MAP Kinases