title: Mu Opioid Receptor Actions in the Lateral Habenula.
abstract: Increased activity of lateral habenula (LHb) neurons is correlated with aversive states including pain, opioid abstinence, rodent models of depression, and failure to receive a predicted reward. Agonists at the mu opioid receptor (MOR) are among the most powerful rewarding and pain relieving drugs. Injection of the MOR agonist morphine directly into the habenula produces analgesia, raising the possibility that MOR acts locally within the LHb. Consequently, we examined the synaptic actions of MOR agonists in the LHb using whole cell patch clamp recording. We found that the MOR selective agonist DAMGO inhibits a subset of LHb neurons both directly and by inhibiting glutamate release onto these cells. Paradoxically, DAMGO also presynaptically inhibited GABA release onto most LHb neurons. The behavioral effect of MOR activation will thus depend upon both the level of intrinsic neuronal activity in the LHb and the balance of activity in glutamate and GABA inputs to different LHb neuronal populations.
authors.affiliation: Department of Neurology, The Wheeler Center for the Neurobiology of Addiction, Alcoholism and Addiction Research Group, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Elyssa B
authors.initials: EB
authors.lastname: Margolis
authors.affiliation: Department of Neurology, The Wheeler Center for the Neurobiology of Addiction, Alcoholism and Addiction Research Group, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Fields
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D019262:Habenula / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid