Uncoupling protein 2 (UCP2) lowers alcohol sensitivity and pain threshold.
Abuse of ethanol is a major risk factor in medicine, in part because of its widespread effect on the activity of the central nervous system, including behavior, pain, and temperature sensation. Uncoupling protein 2 (UCP2) is a mitochondrial protonophore that regulates cellular energy homeostasis. Its expression in mitochondria of axons and axon terminals of basal forebrain areas suggests that UCP2 may be involved in the regulation of complex neuronal responses to ethanol. We employed a paradigm in which acute exposure to ethanol induces tolerance and altered pain and temperature sensation. In UCP2 overexpressing mice, sensitivity to ethanol was decreased compared to that of wild-type animals, while UCP2 knockouts had increased ethanol sensitivity. In addition, UCP2 expression was inversely correlated with the impairment of pain and temperature sensation induced by ethanol. Taken together, these results indicate that UCP2, a mitochondrial uncoupling protein previously associated with peripheral energy expenditure, is involved in the mediation of acute ethanol exposure on the central nervous system. Enhancement of UCP2 activation after acute alcohol consumption might decrease the time of recovery from intoxication, whereas UCP2 inhibition might decrease the tolerance to ethanol.
Horvath
Balazs
B
Department of Anesthesiology & Operative Intensive Medicine, Humboldt University, Charite, Berlin, Germany.
Spies
Claudia
C
Horvath
Gyongyi
G
Kox
Wolfgang J
WJ
Miyamoto
Suzanne
S
Barry
Sean
S
Warden
Craig H
CH
Bechmann
Ingo
I
Diano
Sabrina
S
Heemskerk
Jill
J
Horvath
Tamas L
TL
D000428:Alcohol Drinking; D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D007473:Ion Channels; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012119:Respiration; D000071246:Uncoupling Protein 2
D000700:Analgesics; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D000431:Ethanol