title: Phosphodiesterase regulation of alcohol drinking in rodents.
abstract: Alcohol use disorders are chronically relapsing conditions characterized by persistent drinking despite the negative impact on one's life. The difficulty of achieving and maintaining sobriety suggests that current treatments fail to fully address the underlying causes of alcohol use disorders. Identifying additional pathways controlling alcohol consumption may uncover novel targets for medication development to improve treatment options. One family of proteins recently implicated in the regulation of alcohol consumption is the cyclic nucleotide phosphodiesterases (PDEs). As an integral component in the regulation of the second messengers cyclic AMP and cyclic GMP, and thus their cognate signaling pathways, PDEs present intriguing targets for pharmacotherapies to combat alcohol use disorders. As activation of cAMP/cGMP-dependent signaling cascades can dampen alcohol intake, PDE inhibitors may provide a novel target for reducing excessive alcohol consumption, as has been proposed for PDE4 and PDE10A. This review highlights preclinical literature demonstrating the involvement of cyclic nucleotide-dependent signaling in neuronal and behavioral responses to alcohol, as well as detailing the capacity of various PDE inhibitors to modulate alcohol intake. Together these data provide a framework for evaluating the potential utility of PDE inhibitors as novel treatments for alcohol use disorders.
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA 92037, USA. Electronic address: mlogrip@iupui.edu.
authors.forename: Marian L
authors.initials: ML
authors.lastname: Logrip
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D051379:Mice; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction
chemical_list: D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; C512064:PDE10A protein, rat; C492284:Pde10a protein, mouse; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D006152:Cyclic GMP
keywords: Adenylyl or guanylyl cyclase; Alcohol; PKA or PKG; Phosphodiesterase; cAMP or cGMP