Director: Eric Zorrilla, Ph.D.
The Neuroendocrinology Research Component will focus on testing the overarching hypothesis that excitatory glutamatergic signaling in the amygdala is altered during ethanol withdrawal, partly due to actions of CRF systems and neuronal pentraxin 2 (Narp), and thereby promote negative emotional symptoms and relapse risk during abstinence. Specific Aim 1 will use histochemical techniques in combination with glutamate system-restricted knockdown of CRF1 receptor signaling to test the hypothesis that CRF1-driven increases in glutamatergic signaling that originate from the BLA promotes anxiety-like behavior and ethanol self-administration during withdrawal from chronic intermittent ethanol exposure. Specific Aim 2 will use Narp dominant-negative-mediated knockdown of Narp function and glutamate system-restricted overexpression of the Nptx2 gene to test the hypothesis that Narp, via its facilitation of glutamatergic signaling from the BLA, leads to increased anxiety-like behavior and ethanol self-administration. Specific Aim 3 will use site-specific administration of selective antagonists to test the hypothesis that individual ionotropic or metabotropic glutamate receptor subtypes within the CeA and BLA are involved in the increased anxiety-like behavior and ethanol self-administration associated with alcohol withdrawal. The studies will involve close collaboration with the Roberto/Siggins Electrophysiology Component and rely closely on the Animal Models Core and Viral Vector Core.