Age-Related Memory Impairment Mark G Baxter  Neuron  Volume 40, Issue 4, Pages 669-670 (November 2003) DOI: 10.1016/S0896-6273(03)00715-3

Figure 1 A Greatly Simplified Schematic of PKA Regulation Gs-coupled receptors (such as the dopamine D1 receptor) activate adenylate cyclase (AC), which converts ATP to cyclic AMP (cAMP). cAMP in turn activates PKA, which goes on to have various effects on the neuron, including phosphorylation of CREB (cyclic AMP response element binding protein). Gi-coupled receptors (such as the α2 norepinephrine receptor) inhibit AC, reducing cAMP levels and thence PKA activity. Phosphodiesterase type 4 (PDE4) breaks down cAMP, removing its ability to activate PKA. Ramos et al. (2003) used infusions of either Sp-cAMPS or Rp-cAMPS into prefrontal cortex to directly activate or inhibit (respectively) PKA. Sp-CAMPS impairs working memory in aged rats, and Rp-CAMPS improves it. For systemic studies in aged monkeys, rolipram was used to inhibit PDE4, allowing greater cAMP accumulation and thus greater PKA activation. Rolipram impairs working memory in aged monkeys. Neuron 2003 40, 669-670DOI: (10.1016/S0896-6273(03)00715-3)