title: Molecular Changes in Opioid Addiction: The Role of Adenylyl Cyclase and cAMP/PKA System.
abstract: For centuries, opiate analgesics have had a considerable presence in the treatment of moderate to severe pain. While effective in providing analgesia, opiates are notorious in exerting many undesirable adverse reactions. The receptor targets and the intracellular effectors of opioids have largely been identified. Furthermore, much of the mechanisms underlying the development of tolerance, dependence, and withdrawal have been delineated. Thus, there is a focus on developing novel compounds or strategies in mitigating or avoiding the development of tolerance, dependence, and withdrawal. This review focuses on the adenylyl cyclase and cyclic adenosine 3,5-monophosphate (cAMP)/protein kinase A (AC/cAMP/PKA) system as the central player in mediating the acute and chronic effects of opioids. This chapter also reviews the neuronal adaptive changes in the locus coeruleus, amygdala, periaqueductal gray, and ventral tegmental area induced by acute and chronic actions of opioid because these neuronal adaptive changes in these regions may underlie the behavioral changes observed in opiate users and abusers.
authors.affiliation: Department of Pharmacy and Pharmacy Administration, Western University of Health Sciences, College of Pharmacy, Pomona, California, USA. Electronic address: chanp@westernu.edu.
authors.forename: Patrick
authors.initials: P
authors.lastname: Chan
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, California, USA.
authors.forename: Kabirullah
authors.initials: K
authors.lastname: Lutfy
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D009293:Opioid-Related Disorders / Q000378:metabolism*
chemical_list: D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases
keywords: addiction; adenylyl cyclase; cyclic adenosine 3,5-monophosphate (cAMP); dependence; opioid; protein kinase A; tolerance; withdrawal