Amnestic drugs in the odor span task: Effects of flunitrazepam, zolpidem and scopolamine

Abstract

The odor span task is an incrementing non-matching-to-sample procedure designed to provide an analysis of working memory capacity in rodents. The procedure takes place in an arena apparatus and rats are exposed to a series of odor stimuli in the form of scented lids with the selection of new stimuli reinforced. This procedure makes it possible to study drug effects as a function of the number of stimuli to remember. In the present study, the non-selective positive allosteric GABA_A receptor modulator flunitrazepam impaired odor span performance at doses that did not affect a control odor discrimination. In contrast, the alpha-1 selective positive GABA_A receptor modulator zolpidem and the cholinergic receptor antagonist scopolamine only impaired odor span at doses that produced more global impairment, including decreased accuracy in the control discrimination and increased response omissions in the both the odor span and control discrimination procedures. Even though the effects of flunitrazepam were selective to odor span performance, they did not depend on the number of stimuli to remember-the same degree of impairment occurred regardless of the memory load. These findings suggest that flunitrazepam interfered selectively with conditional discrimination performance rather than working memory and tentatively suggest that flunitrazepam's selective effects in the odor span task relative to the control odor discrimination are mediated by one or more non-alpha1 GABA_A receptor subtypes.

Keywords: Flunitrazepam; GABA-A modulator; Odor span task; Scopolamine; Working memory; Zolpidem.

Figure 1

Top panel shows mean percent correct as a function of flunitrazepam dose for OST (black circles) and SDC (white circles) trials. Lower panel shows mean span length (black circles) and longest run (white circles). Vertical lines indicate SEM.

Figure 2

Top panel shows mean percent correct and omissions as a function of zolpidem dose for OST (black circles) and SDC (white circles) trials. Black bars show percent omissions for OST and white bars show SDC omissions. Lower panel shows mean span length (black circles) and longest run (white circles). Vertical lines indicate SEM.

Figure 3

Top panel shows mean percent correct and omissions as a function of scopolamine dose for OST (black circles) and SDC (white circles) trials. Black bars show percent omissions for OST and white bars show SDC omissions. Lower panel shows mean span length (black circles) and longest run (white circles). Vertical lines indicate SEM.

Figure 4

Normalized percent correct (calculated as percent of vehicle values) for OST (black circles) and SDC (black squares) plotted as a function of log drug dose for flunitrazepam (top), zolpidem (middle) and scopolamine (bottom). Vertical bars indicate SEM.

Figure 5

Percent correct on OST trials plotted as a function of the number of stimuli to remember for the 0.3 mg/kg and 1.0 mg/kg doses of flunitrazepam and vehicle. Vertical lines indicate SEM.