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Effects of Ethanol on Midbrain Neurons: Role of Opioid Receptors
Author(s) -
Xiao Cheng,
Zhang Jingli,
Krnjević Krešimir,
Ye Jiang Hong
Publication year - 2007
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2007.00405.x
Subject(s) - ventral tegmental area , gabaergic , dopaminergic , damgo , chemistry , (+) naloxone , opioid , dopaminergic pathways , neuroscience , enkephalin , opioid receptor , midbrain , dopamine , agonist , pharmacology , receptor , biology , central nervous system , biochemistry
Background: Although ethanol addiction is believed to be mediated by the mesolimbic dopamine system, originating from the ventral tegmental area (VTA), how acute ethanol increases the activity of VTA dopaminergic (DA) neurons remains unclear. Method: Patch‐clamp recordings of spontaneous firings of DA and GABAergic neurons in the VTA in acute midbrain slices from rats. Results: Ethanol (20–80 mM) excites DA neurons, and more potently depresses firing of local GABAergic neurons. The ethanol‐induced excitation of DA neurons is considerably attenuated by DAMGO (Tyr‐ d ‐Ala‐Gly‐ N ‐Me‐Phe‐Gly‐ol enkephalin), a μ ‐opioid agonist that suppresses firing of GABAergic neurons, or by naloxone, a general opioid antagonist. The ongoing opioid‐induced facilitation of DA cell firing (revealed by naloxone) is enhanced by ethanol, probably by an increase in opioid release or action. Conclusion: Ethanol excites VTA DA neurons at least partly by increasing ongoing opioid‐mediated suppression of local GABAergic inhibition. This indirect mechanism may contribute significantly to the positively reinforcing properties of ethanol.