title: The delta opioid receptor antagonist, SoRI-9409, decreases yohimbine stress-induced reinstatement of ethanol-seeking.
abstract: A major problem in treating alcohol use disorders (AUDs) is the high rate of relapse due to stress and re-exposure to cues or an environment previously associated with alcohol use. Stressors can induce relapse to alcohol-seeking in humans or reinstatement in rodents. Delta opioid peptide receptors (DOP-Rs) play a role in cue-induced reinstatement of ethanol-seeking; however, their role in stress-induced reinstatement of ethanol-seeking is not known. The objective of this study was to determine the role of DOP-Rs in yohimbine-stress-induced reinstatement of ethanol-seeking. Male, Long-Evans rats were trained to self-administer 10% ethanol in daily 30-minute operant self-administration sessions using a FR3 schedule of reinforcement, followed by extinction training. Once extinction criteria were met, we examined the effects of the DOP-R antagonist, SoRI-9409 (0-5 mg/kg, i.p.) on yohimbine (2 mg/kg, i.p.) stress-induced reinstatement. Additionally, DOP-R-stimulated [(35) S]GTPγS binding was measured in brain membranes and plasma levels of corticosterone (CORT) were determined. Pre-treatment with SoRI-9409 decreased yohimbine stress-induced reinstatement of ethanol-seeking but did not affect yohimbine-induced increases in plasma CORT levels. Additionally, yohimbine increased DOP-R-stimulated (35) [S]GTPγS binding in brain membranes of ethanol-trained rats, an effect that was inhibited by SoRI-9409. This suggests that the DOP-R plays an important role in yohimbine-stress-induced reinstatement of ethanol-seeking behavior, and DOP-R antagonists may be promising candidates for further development as a treatment for AUDs.
authors.affiliation: Ernest Gallo Clinic and Research Center, University of California San Francisco, 5858 Horton Street, Emeryville, CA, USA.
authors.forename: Carsten K
authors.initials: CK
authors.lastname: Nielsen
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Simms
authors.forename: Jade J
authors.initials: JJ
authors.lastname: Bito-Onon
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Ananthan
authors.forename: Selena E
authors.initials: SE
authors.lastname: Bartlett
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000517:prevention & control*; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D003345:Corticosterone / Q000502:physiology; D003463:Cues; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000378:metabolism; D009022:Morphine Derivatives / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D012055:Reinforcement Schedule; D012646:Self Administration; D013315:Stress, Psychological / Q000523:psychology; D015016:Yohimbine / Q000494:pharmacology*
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D009022:Morphine Derivatives; D011804:Quinolines; D017465:Receptors, Opioid, delta; C425887:SoRI 9409; C094142:TAN 67; D015016:Yohimbine; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D003345:Corticosterone