II. Functional consequences of intragastrically administered ethanol in rats as measured by the 2-[14C]deoxyglucose method: the contribution of dopamine.
As outlined in the companion paper, many of the changes in functional activity produced by acute intragastric ethanol administration as determined by the quantitative autoradiographic 2-[14C]deoxyglucose method occur in structures of the mesocorticolimbic and nigrostriatal dopamine circuits. In this study, a dopaminergic antagonist, flupenthixol, was used to determine the contribution of dopamine to the ethanol-induced increases in functional activity. To assess the ability of flupenthixol to block dopaminergic-induced increases in glucose utilization, it was first examined in conjunction with the indirect dopaminergic agonist methylphenidate. Pretreatment with flupenthixol significantly reduced methylphenidate-induced increases in glucose utilization in structures of the mesocorticolimbic and nigrostriatal dopamine circuits. These findings indicate that this is an effective strategy for the determination of the neurochemical contributions to the changes in CNS functional activity. Flupenthixol pretreatment blocked many of the ethanol-induced increases in glucose utilization at the 0.25 g/kg dose, particularly in mesocorticolimbic and nigrostriatal structures. At the 1.0 and 2.0 g/kg ethanol doses, however, pretreatment with flupenthixol did not reverse the increases in glucose utilization in several brain regions, suggesting that dopaminergic activity is not responsible for the observed increases in glucose utilization and further, that these increases involve other neurotransmitter systems. In some regions, however, flupenthixol pretreatment resulted in augmented levels of glucose utilization above those rates produced by the administration of higher doses of ethanol alone. These findings suggest that the contribution of dopamine to the increases in functional activity are more complex at higher doses of ethanol.
Williams-Hemby
L
L
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1083, USA.
Porrino
L J
LJ
D000284:Administration, Oral; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D002250:Carbon Radioisotopes; D003847:Deoxyglucose; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005475:Flupenthixol / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007441:Intubation, Gastrointestinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects
D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D000431:Ethanol; D003847:Deoxyglucose; D005475:Flupenthixol; D005947:Glucose; D004298:Dopamine