Affective Cue-Induced Escalation of Alcohol Self-Administration and Increased 22-kHz Ultrasonic Vocalizations during Alcohol Withdrawal: Role of Kappa-Opioid Receptors

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 38; no. 4; pp. 647 - 654
• Main Authors: BERGER, Anthony L, WILLIAMS, Angela M, MCGINNIS, Molly M, WALKER, Brendan M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.03.2013
• Subjects: Addictive behaviors; Adult and adolescent clinical studies; Affect (Psychology); Alcohol use; Alcohol withdrawal; Alcoholism; Alcoholism - physiopathology; Alcoholism and acute alcohol poisoning; Animals; Biological and medical sciences; Cocaine; Cues; Dose-Response Relationship, Drug; Drug withdrawal; Drugs; Ethanol - administration & dosage; Laboratory animals; Male; Medical sciences; Narcotics; Neurosciences; Original; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Wistar; Receptors, Opioid, kappa - agonists; Receptors, Opioid, kappa - antagonists & inhibitors; Receptors, Opioid, kappa - physiology; Self Administration; Substance Withdrawal Syndrome - physiopathology; Toxicology; Ultrasonics; Vocalization, Animal - physiology; United States > US; Affect affectivity; Sound production; Alcoholism; operant self-administration; κ Opioid receptor; Self administration; negative affect; alcohol and alcoholism; cues; Alcoholic beverage; kappa-opioid receptor; Disintoxication; ultrasonic vocalizations
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/npp.2012.229

Negative affect promotes dysregulated alcohol consumption in non-dependent and alcohol-dependent animals, and cues associated with negative affective states induce withdrawal-like symptoms in rats. This study was designed to test the hypotheses that: (1) the kappa-opioid receptor (KOR) system mediates phenotypes related to alcohol withdrawal and withdrawal-like negative affective states and (2) cues associated with negative affective states would result in dysregulated alcohol consumption when subsequently presented alone. To accomplish these goals, intracerebroventricular infusion of the KOR antagonist nor-binaltorphimine (nor-BNI) was assessed for the ability to attenuate the increase in 22-kHz ultrasonic vocalizations (USVs) associated with alcohol withdrawal and KOR activation in adult male wistar rats. Furthermore, cues associated with a KOR agonist-induced negative affective state were assessed for the ability to dysregulate alcohol consumption and the efficacy of intracerebroventricular KOR antagonism to reduce such dysregulation was evaluated. KOR antagonism blocked the increased number of 22-kHz USVs observed during acute alcohol withdrawal and a KOR agonist (U50,488) resulted in a nor-BNI reversible increase in 22-kHz USVs (mimicking an alcohol-dependent state). Additionally, cues associated with negative affective states resulted in escalated alcohol self-administration, an effect that was nor-BNI sensitive. Taken together, this study implicates negative affective states induced by both alcohol withdrawal and conditioned stimuli as being produced, in part, by activity of the DYN/KOR system.