The role of the GABAergic and dopaminergic systems in the brain response to an intragastric load of alcohol in conscious rats.
The brain's response to ethanol intake has been extensively investigated using electrophysiological recordings, brain lesion techniques, and c-Fos immunoreactivity. However, few studies have investigated this phenomenon using functional magnetic resonance imaging (fMRI). In the present study, we used fMRI to investigate the blood oxygenation level-dependent (BOLD) signal response to an intragastric (IG) load of ethanol in conscious, ethanol-naive rats. An intragastrically infused 10% ethanol solution induced a significant decrease in the intensity of the BOLD signal in several regions of the brain, including the bilateral amygdala (AMG), nucleus accumbens (NAc), hippocampus, ventral pallidum, insular cortex, and cingulate cortex, and an increase in the BOLD signal in the ventral tegmental area (VTA) and hypothalamic regions. Treatment with bicuculline, which is an antagonist of the gamma-aminobutyric acid A (GABA(A)) receptor, increased the BOLD signal intensity in the regions that had shown decreases in the BOLD signal after the IG infusion of 10% ethanol solution, but it did not affect the BOLD signal increase in the hypothalamus. Treatment with SCH39166, which is an antagonist of D1-like receptors, eliminated the increase in the BOLD signal intensity in the hypothalamic areas but did not affect the BOLD signal decrease following the 10% ethanol infusion. These results indicate that an IG load of ethanol caused both a GABA(A) receptor-mediated BOLD decrease in the limbic system and the cortex and a D1-like receptor-mediated BOLD increase in the hypothalamic regions in ethanol-naive rats.
Tsurugizawa
T
T
Institute of Life Sciences, Ajinomoto Co., Inc., Suzuki-cho 1-1 Kawasaki-ku, Kawasaki 210-8601, Japan.
Uematsu
A
A
Uneyama
H
H
Torii
K
K
D000284:Administration, Oral; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D013997:Time Factors
D001552:Benzazepines; D058787:GABA-A Receptor Antagonists; D017447:Receptors, Dopamine D1; D011963:Receptors, GABA-A; C058081:ecopipam; D000431:Ethanol; D010100:Oxygen; D001640:Bicuculline