title: Endocannabinoid-mediated synaptic plasticity and addiction-related behavior.
abstract: Endogenous cannabinoids (eCBs) are retrograde messengers that provide feedback inhibition of both excitatory and inhibitory transmission in brain through the activation of presynaptic CB₁ receptors. Substantial evidence indicates that eCBs mediate various forms of short- and long-term plasticity in brain regions involved in the etiology of addiction. The present review provides an overview of the mechanisms through which eCBs mediate various forms of synaptic plasticity and discusses evidence that eCB-mediated plasticity is disrupted following exposure to a variety of abused substances that differ substantially in pharmacodynamic mechanism including alcohol, psychostimulants and cannabinoids. The possible involvement of dysregulated eCB signaling in maladaptive behaviors that evolve over long-term drug exposure is also discussed, with a particular focus on altered behavioral responses to drug exposure, deficient extinction of drug-related memories, increased drug craving and relapse, heightened stress sensitivity and persistent affective disruption (anxiety and depression).
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Nimish
authors.initials: N
authors.lastname: Sidhpura
authors.forename: Loren H
authors.initials: LH
authors.lastname: Parsons
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D063388:Endocannabinoids; D006801:Humans; D013287:Illicit Drugs / Q000009:adverse effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D014179:Neurotransmitter Uptake Inhibitors / Q000009:adverse effects; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019966:Substance-Related Disorders / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D013287:Illicit Drugs; D009419:Nerve Tissue Proteins; D014179:Neurotransmitter Uptake Inhibitors; D043884:Receptor, Cannabinoid, CB1