Chunk #44 — 3 Neural Substrates for the Negative Emotional State Associated with Alcoholism — 3.2 Between-System Neuroadaptations that Contribute to Compulsivity Associated with the Dark Side of Alcoholism
Dynorphin, an opioid peptide that binds to κ opioid receptors, has long been known to show activation with chronic administration of psychostimulants and opioids (Nestler 2004; Koob 2008a), and κ opioid receptor agonists produce aversive effects in animals and humans (Mucha and Herz 1985; Pfeiffer et al. 1986). Although κ agonists suppress nondependent drinking, possibly via aversive stimulus effects (Wee and Koob 2010), κ opioid antagonists block the excessive drinking associated with ethanol withdrawal and dependence (Holter et al. 2000; Walker and Koob 2008). Recently, some have argued that the effects of CRF in producing negative emotional states are mediated by activation of κ opioid systems (Land et al. 2008). However, κ receptor activation can activate CRF systems in the spinal cord (Song and Takemori 1992), and there is pharmacological evidence that dynorphin systems can also activate the CRF system. A CRF1, antagonist blocked κ agonist-induced reinstatement of cocaine seeking in squirrel monkeys (Valdez et al. 2007).
