Effect of BMY 21502 on Classical Conditioning of the Eyeblink Response in Young and Older Rabbits

Abstract

BMY 21502, a substituted pyrrolidionone, has been found to enhance a simple form of learning in older rabbits. In humans, this simple type of learning, classical conditioning of the eyeblink response, declines in normal aging and is seriously impaired in Alzheimer's disease (AD). We have demonstrated that eyeblink classical conditioning reliably discriminates patients diagnosed with probable AD from non-demented, age-matched elderly subjects. Older organisms can be classically conditioned, but they condition at a much slower rate than younger organisms. Our preliminary analyses indicate age differences in distribution of protein kinase C in the hippocampus. Here we also report that older rabbits that are administered two different doses of BMY 21502 classically condition at a rate approximating that of young rabbits.

Mecamylamine- or scopolamine-induced learning impairment: ameliorated by nefiracetam

“…We have not tested doses of neÞracetam alone other than 10 mg/kg in young rabbits, and the possibility exists that the optimal dose is di¤erent for young than for older rabbits. The result that neÞracetam did not facilitate acquisition in young rabbits is comparable to our previous observation with eyeblink conditioning in young rabbits treated with another pyrrolidone derivative, BMY 21502 (Woodru¤-Pak et al 1994b). Both neÞracetam and BMY 21502 ameliorated acquisition of the conditioned eyeblink response in older rabbits (Woodru¤-Pak et al 1994a, b), but neither drug facilitated learning in young rabbits.…”

Aging‐related alterations in the distribution of Ca2+‐dependent PKC isoforms in rabbit hippocampus

“…In a preliminary autoradiographic study, Woodruff-Pak et al (1991) (Olds et al, 1989), suggesting a decrease in membrane-associated PKC in old rabbit hippocampus. These results corroborate our findings obtained with Western blotting and immunocytochemical methods.…”

Evaluation of Cognition‐enhancing Drugs: Utility of the Model System of Eyeblink Classical Conditioning

“…We tested the hypothesis that BMY 2 1502 would ameliorate deficits in acquisition of EBCC in older rabbits and possibly enhance acquisition in young rabbits (106). Young and older New Zealand white rabbits were classically conditioned for 10 90trial sessions in the 750 ms delay paradigm using a tone CS and corneal airpuff US.…”