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Effects of benzodiazepine receptor inverse agonists and nicotine on behavioral vigilance in senescent rats.

Authors
  • Turchi, J
  • Holley, L A
  • Sarter, M
Type
Published Article
Journal
The journals of gerontology. Series A, Biological sciences and medical sciences
Publication Date
May 01, 1996
Volume
51
Issue
3
Identifiers
PMID: 8630700
Source
Medline
License
Unknown

Abstract

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.

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