Food restriction induces synaptic incorporation of calcium-permeable AMPA receptors in nucleus accumbens

Eur J Neurosci. 2017 Mar;45(6):826-836. doi: 10.1111/ejn.13528. Epub 2017 Feb 15.


Chronic food restriction potentiates behavioral and cellular responses to drugs of abuse and D-1 dopamine receptor agonists administered systemically or locally in the nucleus accumbens (NAc). However, the alterations in NAc synaptic transmission underlying these effects are incompletely understood. AMPA receptor trafficking is a major mechanism for regulating synaptic strength, and previous studies have shown that both sucrose and d-amphetamine rapidly alter the abundance of AMPA receptor subunits in the NAc postsynaptic density (PSD) in a manner that differs between food-restricted and ad libitum fed rats. In this study we examined whether food restriction, in the absence of reward stimulus challenge, alters AMPAR subunit abundance in the NAc PSD. Food restriction was found to increase surface expression and, specifically, PSD abundance, of GluA1 but not GluA2, suggesting synaptic incorporation of GluA2-lacking Ca2+-permeable AMPARs (CP-AMPARs). Naspm, an antagonist of CP-AMPARs, decreased the amplitude of evoked EPSCs in NAc shell, and blocked the enhanced locomotor response to local microinjection of the D-1 receptor agonist, SKF-82958, in food-restricted, but not ad libitum fed, subjects. Although microinjection of the D-2 receptor agonist, quinpirole, also induced greater locomotor activation in food-restricted than ad libitum fed rats, this effect was not decreased by Naspm. Taken together, the present findings are consistent with the synaptic incorporation of CP-AMPARs in D-1 receptor-expressing medium spiny neurons in NAc as a mechanistic underpinning of the enhanced responsiveness of food-restricted rats to natural rewards and drugs of abuse.

Keywords: addiction; dieting; neuroplasticity; reward.

MeSH terms

  • Animals
  • Benzazepines / pharmacology
  • Calcium / metabolism*
  • Caloric Restriction*
  • Dopamine Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials
  • Male
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Nucleus Accumbens / physiology
  • Post-Synaptic Density / metabolism*
  • Post-Synaptic Density / physiology
  • Quinpirole / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / genetics
  • Receptors, AMPA / metabolism*
  • Receptors, Dopamine D1 / genetics
  • Receptors, Dopamine D1 / metabolism


  • Benzazepines
  • Dopamine Antagonists
  • Receptors, AMPA
  • Receptors, Dopamine D1
  • Quinpirole
  • SK&F 82958
  • glutamate receptor ionotropic, AMPA 2
  • Calcium
  • glutamate receptor ionotropic, AMPA 1