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 GABAA receptor modulator flunitrazepam impaired odor span performance at doses that did not affect a control odor discrimination. In contrast, the alpha-1 selective positive GABAA 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 GABAA receptor subtypes.

Effects of N-Methyl-D-aspartate (NMDA) antagonists ketamine, methoxetamine, and phencyclidine on the odor span test of working memory in rats.

“…For example, the effects of chlordiazepoxide were relatively weak and limited to span length (Galizio et al, 2013). In contrast, flunitrazepam impaired OST accuracy at doses that spared control performances, but these effects did not depend on the number of stimuli to remember (Galizio, Mathews, Mason, Panoz-Brown, Prichard & Soto, 2017). Rather, the effects of flunitrazepam appeared to involve a breakdown of the overall non-matching task.…”

Effects of NMDA antagonist dizocilpine (MK-801) are modulated by the number of distractor stimuli in the rodent odor span task of working memory

“…As rats became successful in retrieving pellets, unscented lids that partially covered the cups were introduced and gradually covered more of the cup until rats had learned to remove lids that completely covered the cups. Rats then began training on the OST incrementing nonmatch-to-sample procedure (see Galizio, et al, 2017;Mathews et al, 2018). Scented lids now covered the cups and a session-novel odorant was presented during each trial along with odorants from previous trials.…”

“…Circular open-field arenas (94 cm in diameter) surrounded by 32 cm high metal baffling (described previously by Galizio, et al, 2017;Mathews, et al, 2018) were used for this experiment. The floor of the arenas included 18 holes, spaced 13.3 cm apart in two concentric circular arrangements with 12 holes in the outside ring and 6 in the inner ring.…”

Characterization and tentative identification of new flunitrazepam metabolites in authentic human urine specimens using liquid chromatography‐Q exactive‐HF hybrid quadrupole‐Orbitrap‐mass spectrometry (LC‐QE‐HF‐MS)

“…Flunitrazepam (FNZ, Figure ) is a fast‐acting benzodiazepine, and it is the most prescribed benzodiazepine, due to its sedative and hypnotic properties. It is used clinically in the treatment of insomnia, muscular tension, anxiety reaction, and the prevention of convulsions . FNZ also has many side effects, including both physical and psychological dependency, decreased sleep quality, damage of balance and speech, respiratory depression or coma, and even death .…”