Rats selected for high ethanol preference (ethanol-preferring “P” rats) show increased anxiety-like behavior and lower levels of p-CREB and neuropeptide Y in the central and medial amygdala when compared with ethanol-nonpreferring “NP” rats.116 P rats show reduced anxiety after voluntary ethanol consumption, whereas NP rats do not. Injection of Sp-cAMPS into the central amygdala of P rats drives levels of ethanol intake, anxiety-like behavior, and amygdala p-CREB toward the lower levels found in NP rats.116 Sp-cAMPS injection does not affect anxiety-like behavior in NP rats. Injection of Rp-cAMPS into the central amygdala of NP rats does increase ethanol consumption and anxiety-like behavior.116 These data show that PKA modulation of ethanol drinking depends on interaction with alleles in P and NP rats that may also be responsible for the levels of drinking for which these animals were selected. Such findings underscore the need to consider pharmacogenomics when developing new treatments for addiction.
