title: Food deprivation facilitates reinstatement of morphine-induced conditioned place preference: Role of intra-accumbal dopamine D2-like receptors in associating reinstatement of morphine CPP with stress.
abstract: The high rate of relapse to drug use is one of the main problems in the treatment of addiction. Stress plays the essential role in drug abuse and relapse; nevertheless, little is known about the mechanisms underlying stress and relapse. Accordingly, the effects of intra-accumbal administration of Sulpiride, as a dopamine D2-like receptor antagonist, on an ineffective morphine dose + food deprivation(FD)- and morphine priming-induced reinstatement of conditioned place preference (CPP). About 104 adult male albino Wistar rats weighing 200-280 g were bilaterally implanted by cannula into the nucleus accumbens (NAc). Subcutaneous (sc) injection of morphine (5 mg kg-1) was used daily during a 3-day conditioning phase. After a 24-hr "off" period following achievement of extinction criterion, rats were tested for FD- and priming-induced reinstatement of morphine CPP by an ineffective (0.5 mg kg-1, sc) and priming (1 mg kg-1, sc) dose of morphine, respectively. In the next experiments, animals received different doses of intra-accumbal Sulpiride (0.25, 1, and 4 µg/0.5 µL saline) bilaterally and were subsequently tested for morphine reinstatement. Our findings indicated that the 24-hr FD facilitated reinstatement of morphine CPP. Furthermore, the D2-like receptor antagonist attenuated the ineffective morphine dose+ FD- and priming-induced reinstatement of morphine CPP dose-dependently. Also, contribution of D2-like receptors in mediation of the ineffective morphine dose+ FD-induced reinstatement of CPP was greater than morphine priming-induced reinstatement of CPP. The role of dopaminergic system in morphine reinstatement through a neural pathway in the NAc provides the evidence that D2-like receptor antagonist can be useful therapeutic targets for reinstatement of morphine CPP.
authors.affiliation: Department of Basic Sciences Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Sadeghzadeh
authors.affiliation: Department of Basic Sciences Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
authors.forename: Vahab
authors.initials: V
authors.lastname: Babapour
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Haghparast
mesh_terms: D000818:Animals; D003214:Conditioning, Classical; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology; D005108:Extinction, Psychological; D005508:Food Deprivation; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000378:metabolism / Q000503:physiopathology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology*; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D009020:Morphine; D013469:Sulpiride
keywords: D2-like receptor; conditioned place preference; drug priming; nucleus accumbens; relapse; reward; stress