title: Do specific NMDA receptor subunits act as gateways for addictive behaviors?
abstract: Addiction to alcohol and drugs is a major social and economic problem, and there is considerable interest in understanding the molecular mechanisms that promote addictive drives. A number of proteins have been identified that contribute to expression of addictive behaviors. NMDA receptors (NMDARs), a subclass of ionotropic glutamate receptors, have been of particular interest because their physiological properties make them an attractive candidate for gating induction of synaptic plasticity, a molecular change thought to mediate learning and memory. NMDARs are generally inactive at the hyperpolarized resting potentials of many neurons. However, given sufficient depolarization, NMDARs are activated and exhibit long-lasting currents with significant calcium permeability. Also, in addition to stimulating neurons by direct depolarization, NMDARs and their calcium signaling can allow strong and/or synchronized inputs to produce long-term changes in other molecules (such as AMPA-type glutamate receptors) which can last from days to years, binding internal and external stimuli in a long-term memory trace. Such memories could allow salient drug-related stimuli to exert strong control over future behaviors and thus promote addictive drives. Finally, NMDARs may themselves undergo plasticity, which can alter subsequent neuronal stimulation and/or the ability to induce plasticity. This review will address recent and past findings suggesting that NMDAR activity promotes drug- and alcohol-related behaviors, with a particular focus on GluN2B subunits as possible central regulators of many addictive behaviors, as well as newer studies examining the importance of non-canonical NMDAR subunits and endogenous NMDAR cofactors.
authors.affiliation: Alcohol and Addiction Research Group, Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: F W
authors.initials: FW
authors.lastname: Hopf
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate
keywords: Activity; NMDA; addiction; alcohol; intake; intoxicant; mechanism; plasticity; receptor; subunit