FG 7142- and restraint-induced alterations in the ataxic effects of alcohol and midazolam in rats are time dependent.

The purpose of this study was to examine whether acute stress exposure would alter the ataxic properties of midazolam or ethanol in rats. Rats were administered either vehicle or FG 7142 (10 mg/kg) and placed back in their home cages, or placed in restraining tubes for 90 min. Three and one-half or 24 h following injection all subjects were then administered an ataxic dose of either ethanol or midazolam and after 10 min, motoric impairment was assessed by rotarod performance. Neither FG 7142 administration nor restraint had an impact on rotarod performance 3-1/2 h later for ethanol nor 24 h later in response to midazolam. However, midazolam-induced ataxia was significantly modified 3-1/2 h following both restraint and FG 7142 exposure. Similarly, at the 24-h time point, both manipulations had a significant effect on ethanol-induced motor incoordination. Importantly, prior exposure to FG 7142 and restraint was without effect on rotarod performance in saline-treated subjects. Functional alterations in behavioral reactivity to low doses of two classes of CNS depressants by the acute stress of restraint and/or FG 7142 administration suggest the anxiogenic nature of these stressors may be the critical factor.