EFFECTS OF BENZODIAZEPINE RECEPTOR INVERSE AGONISTS AND NICOTINE ON BEHAVIORAL VIGILANCE IN SENESCENT RATS

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 brief vi sual signals, whereas their ability to discriminate between longer sig nals and nonsignal events was unaffected. The benzodiazepine receptor (BZR) agonist chlordiazepoxide potently and selectively interacted wit h the effects of age on the relative number of hits. However, negative modulators of GABAergic transmission (ZK 93426 beta-CCtB, 33965) fail ed to attenuate the effects of age on behavioral vigilance. The presen t experiment tested the hypothesis that the performance of senescent a nimals (28 months) is further impaired and thus would allow the demons tration of beneficial effects of BZR inverse agonists or nicotine. How ever, administration of ZK 93426 (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 benefic ially 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 findings point to limitations of no rmal aging as a variable in animal experiments on BZR inverse agonist or nicotine-induced attenuation of cognitive impairments that result f rom cholinergic hypofunction.