Effects of ethanol on midbrain neurons: role of opioid receptors.
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.


METHODS
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 mu-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.


CONCLUSIONS
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.
Xiao
Cheng
C
Department of Anesthesiology, New Jersey Medical School, Newark, NJ 07103-2714, USA.
Zhang
Jingli
J
Krnjević
Kresimir
K
Ye
Jiang Hong
JH
D000437:Alcoholism / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000502:physiology
D018756:GABA Antagonists; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D004298:Dopamine