Biperiden-induced delirium model in rats: a behavioral and electroencephalographic study

In order to elucidate the neural mechanisms of delirium, we administered the anticholinergic drug, biperiden (40 mg/kg i.p.), to 10 adult male Wistar rats and examined the resulting polygraphic recordings, including electroencephalography (EEG), electrooculography (EOG), and electromyography (EMG), for 60 min following injection. EEG data were investigated quantitatively by power spectrum analyses using fast Fourier transformation. Ten male Wistar rats receiving saline (i.p.) were used as the control group.

Treated rats demonstrated two types of alternating behavioral change: a hyperactive and hypoactive state. In the hyperactive state, rapid walking, excessive random sniffing, and retropulsion were observed, with EEG desynchronization (significantly increased alpha1 (8.0-10.0 Hz), alpha2 (10.0-13.0 Hz), and beta (13.0-30.0 Hz) power values), as well as EEG slowing (significantly increased delta (0.5-4.0 Hz) and theta1 (4.0-6.0 Hz) power values): significantly marked rapid eye movement, and increased EMG activity. In the hypoactive state, motor arrest and drowsiness were observed, with prominent EEG slowing (significantly increased delta and theta1 power values): significantly decreased rapid eye movement and moderately decreased EMG activity. On the other hand, the control group did not show any behavioral or polygraphic changes.

The behavioral and polygraphic changes induced by biperiden administration in rats are similar to those of delirium in humans. Therefore, it is proposed that biperiden-treated rats are a good delirium model and the anticholinergic mechanism is one of the potent factors in the development of delirium in humans.