Reversible inhibition of acetylcholine synthesis and behavioural effects caused by 3-bromopyruvate.
3-Bromopyruvate inhibits pyruvate decarboxylase in brain homogenates and causes a 90% drop in acetylcholine tissue content at a concentration of 2 mM. Stereotaxic injection of 3-bromopyruvate into the basal forebrain causes after 7 days a 40% drop of acetylcholine concentration and pyruvate decarboxylase activity in the cortex and hippocampus, and greater decreases at the site of injection. However, values return to normal 18 days after injection. Choline acetyltransferase is partially inhibited only at the site of injection after 7 days. Choline transport and choline concentration are not affected at either 7 or 18 days after injection. Impairments in spontaneous alternation and in retention of passive avoidance were seen only 7 days after the injection. The results suggest that stereotaxic injection of bromopyruvate can induce discrete reversible cholinergic lesions on a time scale useful for behavioural experiments and for comparison with neurodegeneration.
Department of Biochemistry, Institute of Psychiatry, DeCrespigny Park, London, England.
T
T
Arendt
M M
MM
Schugens
R M
RM
Marchbanks
D000109:Acetylcholine / Q000037:antagonists & inhibitors*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002794:Choline / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects; D011767:Pyruvate Decarboxylase / Q000378:metabolism; D011773:Pyruvates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011773:Pyruvates; C017092:bromopyruvate; D011767:Pyruvate Decarboxylase; D002794:Choline; D000109:Acetylcholine