The catecholamines dopamine and noradrenaline via the cAMP–PKA–CREB signaling cascade provide an essential modulatory influence on PFC-dependent behaviors producing an inverted “U-shaped” dose–response influence, whereby moderate levels improve PFC function while either too little or too much catecholamines lead to cognitive impairments [for review, see Ref. (89)]. A number of studies including work in our laboratory (51) have shown that blocking the cAMP–PKA–CREB signaling cascade via local infusion of Rp-cAMPS (a compound known to inhibit CREB phosphorylation) into the PFC prevents the impairing effect of stress or aging on working memory performance, while drugs that increase cAMP–PKA signaling either by direct intra-PFC infusion of the cAMP analog Sp-cAMPS or dopamine D1 receptor agonist or i.p. administration of the phosphodiesterase (PDE) inhibitor Rolipram impair cognitive functions [for reviews, see Ref. (89–91)]. As mentioned above, we recently reported that consumption of an alcohol-containing liquid diet for 6 months followed by a 1-week withdrawal period produces working memory impairment in a T-maze spontaneous alternation task in mice, which persists for at least 6 weeks after the cessation of alcohol intake (31, 47). Moreover,
