Aging-, disease- and medication-related imbalance of central dopaminergic neurons causes functional impairment of cognition and neuropsychological
delirium in humans. We attempted to develop a new
delirium model using the direct
dopamine agonist,
apomorphine, and a choice reaction performance task performed by middle-aged rats. The psychological properties of the model were assessed by determining behavioral measures such as choice reaction time, % correct and % omission.
Apomorphine (0.03-0.3 mg/kg s.c.) produced a dose-dependent impairment of task performance. The dose of 0.1 mg/kg prolonged choice reaction time, decreased % correct and increased % omission, indicating that rats had attentional deficits and a reduced arousal or vigilance but no motor deficits or reduced food motivation. This psychological and behavioral impairment of performance resembled that of clinically defined
delirium. In this model, the
cholinomimetic,
aniracetam (10 mg/kg p.o.), reversed the performance impairment induced by
apomorphine. Its two metabolites,
2-pyrrolidinone (10 and 30 mg/kg p.o.) and N-anisoyl-
gamma-aminobutyric acid (
GABA, 10 mg/kg p.o.), effectively reversed the performance impairment as the intact
drug did. Another
pyrrolidinone derivative,
nefiracetam (10 and 30 mg/kg p.o.), tended to worsen the
apomorphine effect. The
cholinesterase inhibitor,
tacrine (10 mg/kg p.o.), markedly worsened all of the behavioral measures.
Neuroleptics,
haloperidol (0.025 mg/kg s.c.),
tiapride (30 mg/kg p.o.) and
sulpiride (10 and 30 mg/kg p.o.), antagonized the
apomorphine effect. The present results suggest that
apomorphine-induced behavioral disturbances in the choice reaction performance task seems to be a useful
delirium model and
aniracetam may improve
delirium through the action of
2-pyrrolidinone and
N-anisoyl-GABA, presumably by facilitating
dopamine release in the striatum by acting as an
AMPA or
metabotropic glutamate receptor agonist.