Format

Send to

Choose Destination
Neuropsychopharmacology. 2016 Jan;41(2):560-7. doi: 10.1038/npp.2015.183. Epub 2015 Jun 24.

Dissociating Motivational From Physiological Withdrawal in Alcohol Dependence: Role of Central Amygdala κ-Opioid Receptors.

Author information

1
Laboratory of Alcoholism and Addictions Neuroscience, Translational Addiction Research Center, Department of Psychology, Washington State University, Pullman, WA, USA.

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.

PMID:
26105136
PMCID:
PMC5130131
DOI:
10.1038/npp.2015.183
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center