title: The effects of AMPA receptor blockade in the prelimbic cortex on systemic and ventral tegmental area opiate reward sensitivity.
abstract: BACKGROUND
  The medial prefrontal cortex (mPFC) is a key neural region involved in opiate-related reward memory processing. AMPA receptor transmission in the mPFC modulates opiate-related reward memory processing, and chronic opiate exposure is associated with alterations in intra-mPFC AMPA receptor function.
  
  
  OBJECTIVE
  The objectives of this study were to examine how pharmacological blockade of AMPA receptor transmission in the prelimbic (PLC) division of the mPFC may modulate opiate reward memory acquisition and whether opiate exposure state may modulate the functional role of intra-PLC AMPA receptor transmission during opiate reward learning.
  
  
  METHODS
  Using an unbiased conditioned place preference (CPP) procedure in rats, we performed discrete, bilateral intra-PLC microinfusions of the AMPA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione, prior to behavioral morphine CPP conditioning, using sub-reward threshold conditioning doses of either systemic (0.05 mg/kg; i.p.) or intra-ventral tegmental area (VTA) morphine (250 ng/0.5 μl).
  
  
  RESULTS
  We show that, in both opiate-naïve and opiate-dependent states, intra-PLC blockade of AMPA receptor transmission, but not the infralimbic cortex, increases the behavioral reward magnitude of systemic or intra-VTA morphine. This effect is dependent on dopamine (DA)ergic signaling because pre-administration of cis-(Z)-flupenthixol-dihydrochloride (α-flu), a broad-spectrum dopamine receptor antagonist, blocked the morphine-reward potentiating effects of AMPA receptor blockade.
  
  
  CONCLUSIONS
  These findings suggest a critical role for intra-PLC AMPA receptor transmission in the processing of opiate reward signaling. Furthermore, blockade of AMPA transmission specifically within the PLC is capable of switching opiate reward processing to a DA-dependent reward system, independently of previous opiate exposure history.
authors.affiliation: Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: Xavier
authors.initials: X
authors.lastname: De Jaeger
authors.forename: Stephanie F
authors.initials: SF
authors.lastname: Bishop
authors.forename: Tasha
authors.initials: T
authors.lastname: Ahmad
authors.forename: Danika
authors.initials: D
authors.lastname: Lyons
authors.forename: Garye Ami
authors.initials: GA
authors.lastname: Ng
authors.forename: Steven R
authors.initials: SR
authors.lastname: Laviolette
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D012201:Reward; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000523:psychology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; C056723:FG 9041; D009020:Morphine