Scopolamine reversal of nicotine enhanced delayed matching-to-sample performance in monkeys

The basis for the memory enhancing action of nicotine was evaluated in five adult monkeys (Macaca fascicularis) well trained in the performance of a delayed matching-to-sample (DTMS) paradigm. Nicotine (1.25-20 μg/kg, IM) produced a dose-dependent improvement in performance of the task. The optimal dose of nicotine for each monkey also improved performance when the animals were tested 24 h later in the no-drug situation. In the same animals, low doses of scopolamine produced a dose-dependent decrement in DTMS performance. A subthreshold dose (defined by DMTS performance decrement) of scopolamine was administered 20 min prior to the optimal dose of nicotine. Scopolamine pretreatment completely blocked the enhanced performance observed earlier with nicotine. The results of this study are consistent with the hypothesis that the enhanced cognitive performance associated with nicotine is due to central acetylcholine release and subsequent muscarinic receptor stimulation.