title: Involvement of nucleus accumbens AMPA receptor trafficking in augmentation of D- amphetamine reward in food-restricted rats.
abstract: BACKGROUND
  Chronic food restriction (FR) increases behavioral responsiveness to drugs of abuse and associated environments. Pre- and postsynaptic neuroadaptations have been identified in the mesoaccumbens dopamine pathway of FR subjects but the mechanistic basis of increased drug reward magnitude remains unclear.
  
  
  OBJECTIVE
  Effects of FR on basal and D-amphetamine-induced trafficking of AMPA receptor subunits to the nucleus accumbens (NAc) postsynaptic density (PSD) were examined, and AMPA receptor involvement in augmentation of D-amphetamine reward was tested.
  
  
  METHODS
  FR and ad libitum fed (AL) rats were injected with D-amphetamine (2.5 mg/kg, i.p.) or vehicle. Brains were harvested and subcellular fractionation and Western analyses were used to assess AMPA receptor abundance in NAc homogenate and PSD fractions. A follow-up experiment used a curve-shift protocol of intracranial self-stimulation to assess the effect of 1-naphthylacetyl spermine (1-NASPM), a blocker of Ca(2+)-permeable AMPA receptors, on rewarding effects of D-amphetamine microinjected in NAc shell.
  
  
  RESULTS
  FR increased GluA1 in the PSD, and D-amphetamine increased p-Ser845-GluA1, GluA1, GluA2, but not GluA3, with a greater effect in FR than AL rats. D-amphetamine lowered reward thresholds, with greater effects in FR than AL rats, and 1-NASPM selectively reversed the enhancing effect of FR.
  
  
  CONCLUSIONS
  Results suggest that FR leads to increased synaptic incorporation of GluA1 homomers to potentiate rewarding effects of appetitive stimuli and, as a maladaptive byproduct, D-amphetamine. The D-amphetamine-induced increase in synaptic p-Ser845-GluA1, GluA1, and GluA2 may contribute to the rewarding effect of D-amphetamine, but may also be a mechanism of synaptic strengthening and behavior modification.
authors.affiliation: Department of Psychiatry, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
authors.forename: Xing-Xiang
authors.initials: XX
authors.lastname: Peng
authors.forename: Soledad
authors.initials: S
authors.lastname: Cabeza de Vaca
authors.forename: Edward B
authors.initials: EB
authors.lastname: Ziff
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Carr
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005508:Food Deprivation / Q000502:physiology*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000503:physiopathology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012201:Reward; D012653:Self Stimulation; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000697:Central Nervous System Stimulants; D003913:Dextroamphetamine; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D013096:Spermine; C104723:glutamate receptor ionotropic, AMPA 3; C067506:1-naphthylacetylspermine; C104722:glutamate receptor ionotropic, AMPA 2