Cholinergic function and memory: extensive inhibition of choline acetyltransferase fails to impair radial maze performance in rats.
The present study investigated the effects of a potent inhibitor of choline acetyltransferase (ChAT), BW813U, on the choice accuracy of rats in the radial arm maze. BW813U (100 mg/kg, IP) produced a rapid (within 1 hour) and substantial decrease in ChAT activity throughout the brain, ranging from 66% (hippocampus) to 80% (caudate nucleus) that lasted up to 5 days. A single injection (50 mg/kg, IP) into rats with lesions (using ibotenic acid) in the nucleus basalis magnocellularis and medial septal area, decreased ChAT activity by 75% and 60% in the cortex and hippocampus, respectively. Lesioned and unlesioned rats were trained on the radial arm maze until they reached a criterion level of performance. Each rat then received an injection of BW813U (50 or 100 mg/kg, IP). Choice accuracy was not impaired at any time following the injection. The lack of effect on performance may be due to 2 possible factors: The radial maze retention paradigm chosen may not be sufficiently difficult, or the decrease in acetylcholine production was not sufficient to affect behavior. Compensation by non-cholinergic neural systems might account for the insensitivity of the rats to significant cholinergic depletion.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000037:antagonists & inhibitors / Q000502:physiology*; D007051:Ibotenic Acid / Q000633:toxicity; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D010078:Oxazines / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D010078:Oxazines; C050589:BW 813U; D007051:Ibotenic Acid; D002795:Choline O-Acetyltransferase