The delta opioid receptor antagonist, SoRI-9409, decreases yohimbine stress-induced reinstatement of ethanol-seeking

• Published in: Addiction biology Vol. 17; no. 2; pp. 224 - 234
• Main Authors: Nielsen, Carsten K., Simms, Jeffrey A., Bito-Onon, Jade J., Li, Rui, Ananthan, Subramaniam, Bartlett, Selena E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-03-2012
• Subjects: Addiction; Adrenergic alpha-2 Receptor Antagonists - pharmacology; Alcohol Drinking - prevention & control; Alcoholic beverages; Animals; Brain; Conditioning, Operant - drug effects; Corticosterone; Corticosterone - physiology; Cues; delta opioid receptor antagonist; Drug self-administration; Drug-Seeking Behavior - drug effects; Ethanol; ethanol-seeking; Extinction; Guanosine 5'-O-(3-Thiotriphosphate) - metabolism; Male; Mesencephalon - metabolism; Morphine Derivatives - pharmacology; Operant conditioning; Opioid receptors (type delta); Plasma levels; Quinolines - pharmacology; Rats; Rats, Long-Evans; Receptors, Opioid, delta - antagonists & inhibitors; Reinforcement; Reinforcement Schedule; Reinstatement; Self Administration; SoRI-9409; Stress; Stress, Psychological - psychology; stress-induced reinstatement; yohimbine; Yohimbine - pharmacology
• ISSN: 1355-6215; 1369-1600
• DOI: 10.1111/j.1369-1600.2010.00295.x

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 [35S]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.