NEFIRACETAM (DM-9384) - EFFECT ON EYEBLINK CLASSICAL-CONDITIONING IN OLDER RABBITS

The nootropic compound nefiracetam was evaluated in 88 older rabbits i n a 750-ms delay paradigm of eyeblink classical conditioning (EBCC). R abbits (mean age = 28.7 months) were assigned in groups of eight to on e of six conditions in experiment 1: paired tone conditioned stimulus (CS)-corneal airpuff unconditioned stimulus (US) presentations and 1, 3, or 10 mg nefiracetam/kg or sterile saline vehicle; explicitly unpai red CS and US presentations and 3 mg nefiracetam/kg or sterile saline vehicle. Animals in the paired conditions received 10 daily sessions o f 90 paired trials and animals in the unpaired conditions received 10 daily sessions of 180 unpaired CS and US presentations. The six condit ions in experiment 2 were 5, 10, and 15 mg nefiracetam/kg and vehicle in 15 sessions of paired presentations; 10 mg nefiracetam/kg and vehic le in 15 sessions of unpaired conditioning. In both experiments 1 and 2, acquisition measured by trials to learning criterion was significan tly faster at the 10 mg/kg dose of nefiracetam. In the repeated measur es analyses comparing six doses in the paired conditions, all dependen t measures [percentage conditioned responses (CRs), CR amplitude, and response latency] indicated significantly better conditioning in rabbi ts treated with 10 mg nefiracetam/kg, but this dose did not increase m otor responding or responding in the unpaired condition. Nefiracetam f acilitated acquisition of EBCC in older rabbits. EBCC is performed poo rly by older humans and is seriously impaired in Alzheimer's disease. These preclinical data in an animal model with clear parallels in huma ns suggest that nefiracetam may prove effective as a cognition enhance r in clinical trials.