Effects of naltrexone on the ethanol-induced changes in the rat central dopaminergic system.
OBJECTIVE
The opioid antagonist naltrexone may reduce ethanol reward, but the underlying neurochemical mechanisms has yet to be clarified. The afferent projections to the nucleus accumbens from the ventral tegmental area (VTA) provide a potential substrate by which endogenous opioids may modulate the dopaminergic rewarding effects of ethanol. We assessed mRNA levels of tyrosine hydroxylase (TH), a major regulatory enzyme in the dopamine synthesis and levels of dopamine and its metabolites after chronic ethanol administration with and without concomitant naltrexone.


METHODS
Sprague-Dawley rats were exposed to chronic ethanol consumption (5%, 4 weeks) with and without concomitant naltrexone administration. Levels of TH mRNA in the VTA and substantia nigra (SN) and dopamine and its metabolites in the striatum of the rats were measured by in situ hybridization and by high performance liquid chromatography, respectively.


RESULTS
Chronic ethanol consumption increased TH mRNA levels in the VTA, but did not cause any significant change in the SN. With naltrexone treatment, ethanol-induced increase in the TH mRNA level was reduced in the VTA. Chronic ethanol consumption did not cause any change in the levels of dopamine and its metabolites in most brain regions. Only in the striatum, ethanol consumption with naltrexone treatment significantly increases the dopamine level.


CONCLUSIONS
This finding supports the presence of interactions of opioid and dopaminergic systems in the VTA in mediating ethanol reward, and thus naltrexone attenuates the rewarding properties of ethanol by interfering with the ethanol-induced stimulation of the mesolimbic dopaminergic pathway.
Lee
Yong-Kyu
YK
Department of Food and Biotechnology, Dongseo University, Busan, South Korea.
Park
Sung-Woo
SW
Kim
Young-Kyung
YK
Kim
Dai-Jin
DJ
Jeong
Jaeseung
J
Myrick
Hugh
H
Kim
Young-Hoon
YH
D000428:Alcohol Drinking; D000818:Animals; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D017403:In Situ Hybridization; D008297:Male; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism
D009292:Narcotic Antagonists; D012333:RNA, Messenger; D000431:Ethanol; D009271:Naltrexone; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine