title: Comparison of the MK-801-induced appetitive extinction deficit with pressing for reward and associated pERK1/2 staining in prefrontal cortex and nucleus accumbens.
abstract: Administration of the noncompetitive N-methyl-d-aspartate (NMDA)-receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) has been shown to produce extinction deficits on appetitive operant tasks. The present study sought to further explore this by comparing extinction pressing to pressing for the primary reward and examining associated neural correlates to determine if the MK-801 extinction profile resembled the behavioral and neural profile associated with pressing for primary reward. Immunohistochemical labeling of phosphorylated extracellular signal-regulated kinase-1 and -2(pERK1/2) in the prelimbic (PrL) and infralimbic (IL) cortices and nucleus accumbens shell (AcbSh) and core (AcbC) was examined after rewarded or extinction lever pressing conditions. A dose-response curve revealed a within-day extinction deficit following administration of 0.05 mg/kg MK-801. All doses of MK-801 were associated with reduced IL pERK1/2 staining but only the 0.05 mg/kg dose was associated with elevated AcbSh pERK1/2 labeling. Extinction pressing under the influence of MK-801 was elevated compared to that seen during rewarded pressing-whether on MK-801 or saline. Rewarded pressing following saline or MK-801 was associated with elevated pERK1/2 in the PrL with no similar patterns in the MK-801/extinction group. There was more pERK1/2 labeling in the AcbSh of the MK-801 extinction group than any other condition. These data suggest that the MK-801-induced extinction deficit may be due to the combination of an underactive cortical behavioral inhibition system and an overactive AcbSh reward system.
authors.affiliation: Department of Neuroscience, Carleton University, Ottawa, ON K1S 5B6, Canada. matthew_holahan@carleton.ca
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Holahan
authors.forename: Erin P
authors.initials: EP
authors.lastname: Westby
authors.forename: Katrina
authors.initials: K
authors.lastname: Albert
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D012201:Reward
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate