A critical review of effects on ethanol intake of the dynorphin/kappa opioid receptor system in the extended amygdala: From inhibition to stimulation

Alcohol Clin Exp Res. 2023 Apr 11. doi: 10.1111/acer.15078. Online ahead of print.ABSTRACTThe dynorphin (DYN) / kappa opioid receptor (KOR) system has increasingly been investigated as a possible pharmacotherapeutic target for the treatment of alcohol use disorder, but findings on the direction of its effects have been mixed. Activation of KORs by DYN has been shown to be able to elicit dysphoric effects, and while the DYN/KOR system has canonically been considered particularly important in driving intake though negative reinforcement in dependent states, this review highlights that its activity may also oppose the positive reinforcement that drives intake in earlier stages. Both DYN and KORs are concentrated in the extended amygdala, a set of interconnected regions that includes the bed nucleus of the stria terminalis, central nucleus of the amygdala, and nucleus accumbens shell. This review will focus on the role of the DYN/KOR system in the extended amygdala in ethanol use. It will begin by examining the effects of ethanol on expression of DYN/KOR in the extended amygdala, expression of DYN/KOR in alcohol-preferring and -avoiding animals, and effects of knockout of DYN/KOR on ethanol intake. Then, it will examine the effects on ethanol use in both dependent and non-dependent states from systemic pharmacological manipulations of DYN/KOR and from specific manipulation of this system in regions of the extended amygdala. The hypothesis proposed is that greater expression and b...

Source: Alcoholism, Clinical and Experimental Research - April 12, 2023 Category: Addiction Authors: Breanne E Pirino Abigail M Kelley Anushree N Karkhanis Jessica R Barson Source Type: research