Abstract
Alcoholism is a chronic relapsing disorder characterized by continued alcohol use despite numerous adverse consequences. Alcohol has been shown to interact with numerous neurotransmitter systems to exert its pharmacological effects. The endogenous opioid system (EOS) has been strongly implicated in the positive and negative reinforcing effects of alcohol. Traditionally recognized as dysphoric/anhedonic in nature, the dynorphin/kappa-opioid receptor (DYN/KOR) system has recently received considerable attention due to evidence suggesting that an upregulated DYN/KOR system may be a critical contributor to the complex factors that result in escalated alcohol consumption once dependent. The present review will discuss alcohol-induced plasticity in the DYN/KOR system and how these neuroadaptations could contribute to excessive alcohol seeking and consumption.
Highlights
Alcohol use disorders, comprising alcohol abuse and dependence, pose a substantial physical, mental, and fiscal health risk to millions of people each year in the US, causing an average of 79,000 deaths and costing $224 billion annually (Grant et al, 2004; Bouchery et al, 2011)
The results suggest that epigenetic plasticity in the dynorphin/kappa-opioid receptor (DYN/KOR) system may be involved in mediating some of the behavioral effects produced following chronic alcohol exposure
An upregulated DYN/KOR system in various key brain regions at proximal (DYN/KOR mRNA and expression) and intermediate (CREB/ FosB/Brain- derived neurotropic factor (BDNF) mediated signaling) levels could contribute to altered distal events in alcohol dependence
Summary
Alcohol use disorders, comprising alcohol abuse and dependence, pose a substantial physical, mental, and fiscal health risk to millions of people each year in the US, causing an average of 79,000 deaths and costing $224 billion annually (Grant et al, 2004; Bouchery et al, 2011). The endogenous opioid system (EOS) has proven to be important when considering the positive reinforcing effects of alcohol. Acute alcohol stimulates the release of β-endorphin (βEND), enkephalin (ENK), and dynorphin (DYN) (Gianoulakis et al, 1996; Marinelli et al, 2003, 2004, 2005, 2006; Dai et al, 2005; Lam et al, 2008; Jarjour et al, 2009). ΒEND and ENK, endogenous ligands for μ-(MOR) and δ-(DOR) opioid receptors, respectively, have been linked to euphoric and positive reinforcing effects of alcohol (Stromberg et al, 1998; Hyytia and Kiianmaa, 2001). DYN, the endogenous ligand for the κ-opioid receptors (KORs) (Chavkin et al, 1982), has been shown to produce aversive effects related to alcohol challenge (Lindholm et al, 2001). The KOR is the preferential binding site for DYN (Chavkin et al, 1982; Merg et al, 2006), DYN has affinity for all three opioid receptors (Merg et al, 2006; Schwarzer, 2009)
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