Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Vol 51, Issue 3 B225-B231, Copyright © 1996 by The Gerontological Society of America
Effects of benzodiazepine receptor inverse agonists and nicotine on behavioral vigilance in senescent rats
J Turchi, LA Holley and M Sarter
Department of Psychology, Ohio State University, Columbus, USA.
Previous experiments demonstrated that, compared with 6-month-old rats, the
performance of 20-month-old rats in a behavioral vigilance task was
characterized by an impairment in their ability to detect visual signals,
whereas their ability to discriminate between longer signals and nonsignal
events was unaffected. The benzodiazepine receptor (BZR) agonist
chlordiazepoxide potently and selectively interacted with the effects of
age on the relative number of hits. However, negative modulators of
GABAergic transmission (Zk 93 426, beta-CCtB, RU 33965) failed to attenuate
the effects of age on behavioral vigilance. the present experiment tested
the hypothesis that the performance of senescent animals (28 months) is
further impaired and thus would allow the demonstration of beneficial
effects of BZR inverse agonists or nicotine. However, administration of ZK
93 426 (0.39, 1.56, 6.25 mg/kg), Ru 33965 (0.1, 0.5 mg/kg), or nicotine
(0.09, 0.287, 0.689 mg/kg) did not beneficially affect the performance of
senescent animals; rather, detrimental effects were found. Considering the
beneficial behavioral effects of these compounds in animals with
experimentally induced impairments in cholinergic function, the present
finding point to limitations of normal aging as a variable in animal
experiments on BZR inverse agonist or nicotine-induced attenuation of
cognitive impairments that result from cholinergic hypofunction.
