title: Dissociating Motivational From Physiological Withdrawal in Alcohol Dependence: Role of Central Amygdala κ-Opioid Receptors.
abstract: Chronic intermittent alcohol vapor exposure leads to increased dynorphin (DYN) A-like peptide expression and heightened kappa-opioid receptor (KOR) signaling in the central nucleus of the amygdala (CeA) and these neuroadaptive responses differentiate alcohol-dependent from non-dependent phenotypes. Important for therapeutic development efforts is understanding the nature of the stimulus that drives dependence-like phenotypes such as escalated alcohol self-administration. Accordingly, the present study examined the impact of intra-CeA KOR antagonism on escalated operant alcohol self-administration and physiological withdrawal symptoms during acute withdrawal and protracted abstinence in rats previously exposed to chronic intermittent alcohol vapor. Following operant training, rats were implanted with intra-CeA guide cannula and exposed to long-term intermittent alcohol vapor exposure that resulted in escalated alcohol self-administration and elevated physiological withdrawal signs during acute withdrawal. Animals received intra-CeA infusions of the KOR antagonist nor-binaltorphimine (nor-BNI; 0, 2, 4, or 6 μg) prior to operant alcohol self-administration sessions and physiological withdrawal assessment during acute withdrawal and protracted abstinence. The results indicated that site-specific KOR antagonism in the CeA ameliorated escalated alcohol self-administration during both acute withdrawal and protracted abstinence test sessions, whereas KOR antagonism had no effect on physiological withdrawal scores at either time point. These results dissociate escalated alcohol self-administration from physiological withdrawal symptoms in relation to KOR signaling in the CeA and help clarify the nature of the stimulus that drives escalated alcohol self-administration during acute withdrawal and protracted abstinence.
authors.affiliation: Laboratory of Alcoholism and Addictions Neuroscience, Translational Addiction Research Center, Department of Psychology, Washington State University, Pullman, WA, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Kissler
authors.affiliation: Laboratory of Alcoholism and Addictions Neuroscience, Translational Addiction Research Center, Department of Psychology, Washington State University, Pullman, WA, USA.
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Walker
mesh_terms: D000281:Administration, Intranasal; D000437:Alcoholism / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology*; D000818:Animals; D066274:Central Amygdaloid Nucleus / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage; D008297:Male; D009042:Motivation / Q000187:drug effects / Q000502:physiology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology*
chemical_list: D002492:Central Nervous System Depressants; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; C051843:binaltorphimine; D000431:Ethanol; D009271:Naltrexone