Recent pharmacological and genetic studies have provided additional evidence for the importance of the cAMP/PKA system in regulating the neurobiological responses to ethanol. PKA inhibition (using micro-infusions of the PKA inhibitor Rp diastereomer of adenosine 3′,5′-cyclic mono-phosphorothioate, Rp-cAMPS) in the central amygdala prevents the development of anxiety in rats during ethanol withdrawal (Pandey et al. 2003). Other studies have shown that the PKA signaling pathway plays an important role in the modulation of several ethanol-induced behavioral actions such as loss of righting reflex (Maas et al. 2005; Thiele et al. 2000). For example, PKA regulatory RIIβ subunit mutant mice, which exhibit lower total cAMP-stimulated PKA activity, are less sensitive to the sedative-hypnotic effects of ethanol as assessed by the loss of righting reflex test (Lai et al. 2007). Furthermore, in vivo studies show that mutant Drosophila lacking production of the RII subunit of PKA are resistant to the intoxicating effects of ethanol (Park et al. 2000). In addition, PKA has been shown to alter GABAA receptor function. For example, PKA activation causes a decrease in GABA-activated currents in cultured cerebellar
