Cognitive effects of scopolamine on temporal preparation in male macaque monkeys

Abstract

Temporal preparation refers to the cognitive ability to anticipate the timing of future events. In a simple reaction time task (SRTT), temporal preparation encompasses foreperiod and sequential effects, which serve as indices of temporal attentional function and short-term memory function, respectively. A previous positron emission tomography (PET) study demonstrated muscarinic cholinergic receptor (mAChR) occupancy by the antagonist scopolamine (0.01 mg/kg) in monkeys, with maximal receptor occupancy and short-term memory impairment observed 120 minutes post-administration. This study aimed to evaluate the effects of scopolamine on temporal preparation at this critical time point. Using the SRTT, reaction times (RTs) were assessed in three monkeys 120 minutes after scopolamine administration (0.01 mg/kg). Additionally, PET imaging with the dopamine D1 receptor radioligand ([¹¹C]SCH23390) was performed in the same monkeys under awake conditions to examine dopamine transmission, given scopolamine’s known interaction with dopaminergic systems. Behavioral results indicated that scopolamine administration decreased average RTs while preserving the foreperiod effect. PET imaging revealed a significant increase in dopamine D1 receptor binding within the putamen following scopolamine administration. To the best of our knowledge, this is the first study to report a reduction in RTs post-scopolamine administration in monkeys. The observed shortening of RTs may result from the interaction between scopolamine-induced short-term memory impairment and enhanced dopamine D1 receptor transmission.