Chronic ethanol ingestion produces cholinergic hypofunction in rat brain.
Alterations in cholinergic function due to prolonged ethanol exposure (up to 9 months) were assessed by choline acetyltransferase (ChAT) activity and high-affinity choline uptake (HAChU) in three brain regions of the Long-Evans rat: frontal cortex, parietal cortex, and region of the nucleus basalis of Meynert (NbM). No statistically significant changes were found in ChAT activity in the 3-month group; however, ChAT activity was decreased in both the frontal cortex (-32%) and NbM region (-22%) after 6 months of ethanol exposure. ChAT activity in the parietal cortex was increased 30% after 6 months. Nine months of exposure significantly decreased ChAT activity in all three brain regions. No significant differences were observed in high-affinity choline uptake after 3 months of ethanol exposure. However, after 6 months of ethanol exposure HAChU was decreased to 51% of control values in the frontal cortex. There was a simultaneous increase in HAChU to 43% and 178% of control values in the NbM and parietal cortex, respectively. However, choline uptake was significantly decreased in the frontal cortex and NbM region after 9 months of exposure. The results indicate a neurotoxic effect of prolonged intake of ethanol on the basal forebrain cholinergic projection system, which may cause impairment of cholinergic innervation of target areas of the basal nucleus complex.
Floyd
E A
EA
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
Young-Seigler
A C
AC
Ford
B D
BD
Reasor
J D
JD
Moore
E L
EL
Townsel
J G
JG
Rucker
H K
HK
D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects; D002794:Choline / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003864:Depression, Chemical; D005625:Frontal Lobe / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000201:enzymology; D010296:Parietal Lobe / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D013377:Substantia Innominata / Q000187:drug effects / Q000201:enzymology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
D002795:Choline O-Acetyltransferase; D002794:Choline