CHOLINERGIC IMPROVEMENT OF A NATURALLY-OCCURRING MEMORY DEFICIT IN THE YOUNG-RAT

In a single-trial, passive-avoidance response (PAR) paradigm, young ra ts at post-natal day (PND) 16 were found to exhibit a performance defi cit that diminished progressively with age. When administered prior to training, single peripheral. injections of cholinomimetic drugs, eith er a muscarinic agonist (arecoline, pilocarpine or oxotremorine), an a cetylcholinesterase inhibitor (tacrine or E2020), or nicotine, increas ed the response latencies for young rats to that of adult levels in a dose-dependent manner (overall dose range=0.003 mu g/kg-10 mg/kg). Nei ther the cholinergic antagonists scopolamine, atropine or mecamylamine , nor a series of non-cholinergic drugs, diazepam, haloperidol, phenob arbital, pargyline, D-amphetamine, imipramine, piracetam or N-methyl-D -aspartate (NMDA) increased PAR latencies. When 0.1 mg/kg scopolamine was given to young rats prior to arecoline, the dose-effect curve for enhanced latency times was shifted to the right. Higher doses of scopo lamine completely blocked the effects of arecoline. Scopolamine (0.001 -1.0 mg/kg) administered subsequent to, rather than before PAR trainin g, blocked the usual arecoline-induced enhancement of response latenci es. Alternatively, consolidation could be facilitated with different d oses of tacrine (0.0003-10 mg/kg). These results demonstrate that youn g rats fail to remember the PAR but that retention for this task can b e specifically enhanced with cholinomimetic drugs.