Cholinergic-rich brain transplants reverse alcohol-induced memory deficits.
Alcohol-induced memory impairment in man has been attributed to deficiencies in subcortical noradrenergic and cholinergic systems, as well as to damage in midbrain structures. Korsakoff's psychosis, a disease in which alcohol poisoning causes apparently irreversible memory defects, is characterized by lesions in cholinergic and noradrenergic nuclei and by a decrease in the activity of choline acetyltransferase (ChAT) and the content of noradrenaline (NA) in forebrain areas such as cerebral cortex and hippocampus, innervated by these nuclei. Prolonged intake of ethanol in rodents similarly produces signs of noradrenergic and cholinergic deafferentation in the cortex and hippocampus, as well as persistent memory deficits. To test whether alcohol-induced memory impairments depend on cholinergic deafferentation, we transplanted cholinergic-rich fetal basal forebrain cell suspensions into the cortex and hippocampus of alcohol-treated rats. The substantial and persistent memory losses produced in our rats by ethanol intake were associated with an impairment of cholinergic function, and were reversed by cholinergic-rich transplants into cortex and hippocampus.
Arendt
T
T
Department of Psychology, Institute of Psychiatry, Denmark Hill, London, UK.
Allen
Y
Y
Sinden
J
J
Schugens
M M
MM
Marchbanks
R M
RM
Lantos
P L
PL
Gray
J A
JA
D000109:Acetylcholine / Q000502:physiology*; D000110:Acetylcholinesterase / Q000032:analysis; D000647:Amnesia / Q000139:chemically induced / Q000628:therapy*; D000818:Animals; D002540:Cerebral Cortex / Q000601:surgery; D000431:Ethanol / Q000633:toxicity*; D006624:Hippocampus / Q000601:surgery; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D009417:Nerve Tissue / Q000637:transplantation; D051381:Rats; D011919:Rats, Inbred Strains
D000431:Ethanol; D000110:Acetylcholinesterase; D000109:Acetylcholine