There is also evidence for interaction between the DYN/KOR system and CRF within extended amygdala circuitry that have implications for stress and chronic alcohol consequences. For example, these neuropeptides have been shown to be involved in chronic alcohol-induced alterations in synaptic plasticity in the CeA (Kang-Park et al., 2013, 2015; Roberto et al., 2010). Specifically, KORs were shown to modulate GABAergic transmission in a CRF1 receptor-dependent manner (Kang-Park et al., 2015). Interestingly, CRF infusion into the CeA was reported to increase DYN release in a CRF2 receptor-dependent manner (Lam and Gianoulakis, 2011). The aversive/anxiety-like behavioral effects of central CRF administration are attenuated by pretreatment with a KOR antagonist (Bruchas and Chavkin, 2010; Bruchas et al., 2010; Land et al., 2008). Conversely, a CRF1 receptor antagonist blocked KOR agonist-induced reinstatement of alcohol seeking (Funk et al., 2014). Thus, while the precise nature of DYN/KOR-CRF interactions is not completely understood, behavioral and physiological evidence suggests that an interaction between these two stress-related neuropeptide systems within extended amygdala circuitry plays a significant role in mediating stress and motivational effects of chronic alcohol exposure.
