Augmentation of Heroin Seeking Following Chronic Food Restriction in the Rat: Differential Role for Dopamine Transmission in the Nucleus Accumbens Shell and Core

Neuropsychopharmacology. 2017 Apr;42(5):1136-1145. doi: 10.1038/npp.2016.250. Epub 2016 Nov 8.


Caloric restriction during drug abstinence increases the risk for relapse in addicts. In rats, chronic food restriction during a period of withdrawal following heroin self-administration augments heroin seeking. The mechanisms underlying this effect are largely unknown. Here, we investigated the role of nucleus accumbens (NAc) shell and core dopamine (DA) in food restriction-induced augmentation of heroin seeking. Rats were trained to self-administer heroin (0.1 mg/kg/infusion) for 10 days. Next, rats were moved to the animal colony for a withdrawal period, during which rats were food restricted to 90% of their original body weight (FDR group) or given unrestricted access to food (sated group). On day 14 of food restriction, rats were returned to the operant conditioning chambers for a heroin-seeking test under extinction conditions. Extracellular DA levels were assessed using in vivo microdialysis. In separate experiments, the DA D1-like receptor antagonist SCH39166 (12.5, 25.0, or 50.0 ng/side) was administered into the NAc before the heroin-seeking test. In the NAc shell, pre-test exposure to the heroin-associated context increased DA only in FDR rats; but in the NAc core, DA increased regardless of feeding condition. Food restriction significantly augmented heroin seeking and increased DA in the NAc shell and core during the test. Intra-NAc shell administration of SCH39166 decreased heroin seeking in all rats. In contrast, in the NAc core, SCH39166 selectively decreased the augmentation of heroin-seeking induced by chronic food restriction. Taken together, these results suggest that activation of the DA D1-like receptor in the NAc core is important for food restriction-induced augmentation of heroin seeking.

MeSH terms

  • Animals
  • Benzazepines / administration & dosage
  • Dopamine / metabolism*
  • Dopamine Antagonists / administration & dosage
  • Drug-Seeking Behavior*
  • Eating
  • Energy Intake
  • Food Deprivation*
  • Heroin / administration & dosage*
  • Male
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism*
  • Rats, Long-Evans
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D1 / physiology
  • Self Administration


  • Benzazepines
  • Dopamine Antagonists
  • Receptors, Dopamine D1
  • ecopipam
  • Heroin
  • Dopamine