Augmentation of Heroin Seeking Following Chronic Food Restriction in the Rat: Differential Role for Dopamine Transmission in the Nucleus Accumbens Shell and Core.
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.
Department of Psychology, Center for Studies in Behavioral Neurobiology/Groupe de Recherche en Neurobiologie Comportementale, Concordia University, Montreal, QC, Canada.
Tracey M
TM
D'Cunha
Department of Psychology, Center for Studies in Behavioral Neurobiology/Groupe de Recherche en Neurobiologie Comportementale, Concordia University, Montreal, QC, Canada.
Emilie
E
Daoud
Department of Psychology, Center for Studies in Behavioral Neurobiology/Groupe de Recherche en Neurobiologie Comportementale, Concordia University, Montreal, QC, Canada.
Damaris
D
Rizzo
Department of Psychology, Center for Studies in Behavioral Neurobiology/Groupe de Recherche en Neurobiologie Comportementale, Concordia University, Montreal, QC, Canada.
Audrey B
AB
Bishop
Department of Psychology, Center for Studies in Behavioral Neurobiology/Groupe de Recherche en Neurobiologie Comportementale, Concordia University, Montreal, QC, Canada.
Melissa
M
Russo
Department of Psychology, Center for Studies in Behavioral Neurobiology/Groupe de Recherche en Neurobiologie Comportementale, Concordia University, Montreal, QC, Canada.
Gabrielle
G
Mourra
Department of Psychology, Center for Studies in Behavioral Neurobiology/Groupe de Recherche en Neurobiologie Comportementale, Concordia University, Montreal, QC, Canada.
Laurie
L
Hamel
Department of Psychology, Center for Studies in Behavioral Neurobiology/Groupe de Recherche en Neurobiologie Comportementale, Concordia University, Montreal, QC, Canada.
Firas
F
Sedki
Department of Psychology, Center for Studies in Behavioral Neurobiology/Groupe de Recherche en Neurobiologie Comportementale, Concordia University, Montreal, QC, Canada.
Uri
http://orcid.org/0000-0002-7860-6016
U
Shalev
D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000008:administration & dosage; D058999:Drug-Seeking Behavior; D004435:Eating; D002149:Energy Intake; D005508:Food Deprivation; D003932:Heroin / Q000008:administration & dosage*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D020318:Rats, Long-Evans; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology; D012646:Self Administration
D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C058081:ecopipam; D003932:Heroin; D004298:Dopamine