Zolpidem-induced changes in activity, metabolism, and anxiety in rats

Gamma aminobutyric acid (GABA)-A receptor modulators constitute the majority of clinically relevant sedative-hypnotics. Zolpidem (Ambien) is a nonbenzodiazepine GABA-A receptor modulator that binds with high affinity to GABA-A receptors expressing alpha-1 subunits. The present study examined the effects of a new approach to the oral administration of zolpidem on locomotor activity, body weight, food intake, relative food intake, feed efficiency, anxiety, and visceral adiposity in rats. Effects of withdrawal associated with cessation of the drug were also recorded. A daily chronically administered oral 10 mg/kg dose of zolpidem caused a decrease in locomotor activity, an increase in food intake and relative food intake, and a more positive feed efficiency during the drug-administration period. Anxiety and visceral adiposity also increased in animals receiving the drug. During withdrawal of zolpidem, there was a decrease in body weight, food intake, relative food intake, and anxiety, as well as a negative feed efficiency. These results suggest that zolpidem can modulate locomotor activity, metabolism, and anxiety-related behavior. A highly positive feed efficiency and increased visceral adiposity associated with zolpidem intake were unique findings of this study. (C) 2011 Elsevier Inc. All rights reserved.