Scopolamine model of delirium in rats and reversal of the performance impairment by aniracetam

Abstract

Scopolamine causes functional impairment of cognition and neuropsychological delirium in humans. We attempted to develop a scopolamine model of delirium in middle-aged rats using a choice reaction performance task (CRP). Psychological properties were assessed by behavioral measures such as choice reaction time (CRT), percent correct, percent omission, and premature response. Scopolamine (0.3 mg/kg ip) produced an impairment of the task performance observed as a prolongation in CRT, decrease in percent correct, and increase in percent omission, indicating attentional deficits and a reduced arousal or vigilance. The performance impairments in rats seemed to resemble delirium seen in healthy subjects loaded with scopolamine and in patients with dementia, both behaviorally and psychologically. In this model, aniracetam (10 mg/kg po) reversed all of the performance impairments and two (N-anisoyl-GABA and p-anisic acid: 30 mg/kg po) of the three major metabolites acted on the performance impairments effectively. Tacrine tended to decrease only the percent omission at an impairing dose (10 mg/kg po). Haloperidol showed no improvement at a nonimpairing dose (0.025 mg/kg sc) and rather worsened several measures at an impairing dose (0.05 mg/kg sc). Only 2-pyrrolidinone (0.1 μM) of the metabolites enhanced in vitro [3H]-pirenzepine binding to the rat pons-midbrain. The present results suggest that scopolamine-induced behavioral disturbances in the CRP task seems to be a useful delirium model, and aniracetam may improve the delirium-like state through an additional or combined effect of its major metabolites. 2-Pyrrolidinone, at least in part, might facilitate muscarinic M1 receptor function at the mesopontine area. Drug Dev. Res. 43:85–97, 1998. © 1998 Wiley-Liss, Inc.