title: Neuronal extracellular signal-regulated kinase (ERK) activity as marker and mediator of alcohol and opioid dependence.
abstract: Early pioneering work in the field of biochemistry identified phosphorylation as a crucial post-translational modification of proteins with the ability to both indicate and arbitrate complex physiological processes. More recent investigations have functionally linked phosphorylation of extracellular signal-regulated kinase (ERK) to a variety of neurophysiological mechanisms ranging from acute neurotransmitter action to long-term gene expression. ERK phosphorylation serves as an intracellular bridging mechanism that facilitates neuronal communication and plasticity. Drugs of abuse, including alcohol and opioids, act as artificial yet powerful rewards that impinge upon natural reinforcement processes critical for survival. The graded progression from initial exposure to addiction (or substance dependence) is believed to result from drug- and drug context-induced adaptations in neuronal signaling processes across brain reward and stress circuits following excessive drug use. In this regard, commonly abused drugs as well as drug-associated experiences are capable of modifying the phosphorylation of ERK within central reinforcement systems. In addition, chronic drug and alcohol exposure may drive ERK-regulated epigenetic and structural alterations that underlie a long-term propensity for escalating drug use. Under the influence of such a neurobiological vulnerability, encountering drug-associated cues and contexts can produce subsequent alterations in ERK signaling that drive relapse to drug and alcohol seeking. Current studies are determining precisely which molecular and regional ERK phosphorylation-associated events contribute to the addiction process, as well as which neuroadaptations need to be targeted in order to return dependent individuals to a healthy state.
authors.affiliation: Department of Molecular and Cellular Neuroscience, The Scripps Research Institute La Jolla, CA, USA.
authors.forename: Eva R
authors.initials: ER
authors.lastname: Zamora-Martinez
authors.affiliation: Department of Physiology and Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center New Orleans, LA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Edwards
keywords: addiction; amygdala; drug dependence; extracellular signal-regulated kinase; nucleus accumbens; protein phosphorylation; reward; withdrawal