Enhanced incentive motivation in obesity-prone rats is mediated by NAc core CP-AMPARs

Neuropharmacology. 2018 Mar 15;131:326-336. doi: 10.1016/j.neuropharm.2017.12.039. Epub 2017 Dec 29.


Studies in humans suggest that stronger incentive motivational responses to Pavlovian food cues may drive over-consumption leading to and maintaining obesity, particularly in susceptible individuals. However, whether this enhanced incentive motivation emerges as a consequence of obesity or rather precedes obesity is unknown. Moreover, while human imaging studies have provided important information about differences in striatal responsiveness between susceptible and non-susceptible individuals, the neural mechanisms mediating these behavioral differences are unknown. The Nucleus Accumbens (NAc) mediates cue-triggered reward seeking and activity in the NAc is enhanced in obesity-susceptible populations. Therefore here, we used selectively-bred obesity-prone and obesity-resistant rats to examine intrinsic differences in incentive motivation, and the role of NAc AMPARs in the expression of these behaviors prior to obesity. We found that obesity-prone rats exhibit robust cue-triggered food-seeking (Pavlovian-to-instrumental transfer, PIT). Using intra-NAc infusion of AMPAR antagonists, we show that this behavior is selectively mediated by CP-AMPARs in the NAc core. Additionally, biochemical data suggest that this is due in part to experience-induced increases in CP-AMPAR surface expression in the NAc of obesity-prone rats. In contrast, in obesity-resistant rats PIT was weak and unreliable and training did not increase NAc AMPAR surface expression. Collectively, these data show that food cues acquire greater incentive motivational control in obesity-susceptible populations prior to the development of obesity. This provides support to the idea that enhanced intrinsic incentive motivation may be a contributing factor, rather than a consequence of obesity. In addition, these data demonstrate a novel role for experience-induced up-regulation of NAc CP-AMPARs in PIT, pointing to potential mechanistic parallels between the processes leading to addiction and to obesity.

Keywords: AMPA receptor; Addiction; Glutamate plasticity; Motivation; PIT; Striatum.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Appetitive Behavior / drug effects
  • Appetitive Behavior / physiology
  • Behavior, Addictive / metabolism
  • Calcium / metabolism
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology
  • Cues
  • Disease Resistance
  • Genetic Predisposition to Disease
  • Male
  • Motivation / drug effects
  • Motivation / physiology*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Obesity / metabolism*
  • Obesity / psychology*
  • Rats
  • Receptors, AMPA / antagonists & inhibitors
  • Receptors, AMPA / metabolism*
  • Species Specificity
  • Transfer, Psychology / drug effects
  • Transfer, Psychology / physiology


  • Receptors, AMPA
  • Calcium