Further evidence for the predictive validity of the unstable elevated exposed plus-maze, a behavioural model of extreme anxiety in rats: differential effects of fluoxetine and chlordiazepoxide.

The unstable elevated exposed plus-maze (UEEPM) is a novel model of extreme anxiety which elicits unconditioned flight/escape behaviour in rats. The current studies aimed to investigate further the predictive validity of the paradigm, by examining the effects on UEEPM behaviour of both clinically effective (chronic fluoxetine) and ineffective (acute fluoxetine and chlordiazepoxide) treatments for panic disorder. In the first experiment, male Brown Norway rats received a single injection of fluoxetine (1.0-10.0 mg/kg p.o.) or chlordiazepoxide (CDP, 1.0-10.0 mg/kg i.p.) 30 min prior to UEEPM exposure. In the second experiment, in order to assess the effects of chronic dosing or handling on baseline UEEPM behaviour, subjects received either 21 days vehicle injection (p.o.) or handling, before being exposed to the test. Finally, rats received 21 days fluoxetine (1.0-10.0 mg/kg) in their food, before being tested in the UEEPM. Acute CDP and fluoxetine had no effect on UEEPM behaviour. Chronic handling and vehicle administration (p.o.) significantly reduced escape in the UEEPM, hence preventing the effects of chronic fluoxetine administration from being investigated by p.o. dosing. Chronic fluoxetine in subjects' food (10.0 mg/kg) significantly attenuated animals' propensity to escape from the UEEPM. The results further support the pharmacological similarity between symptoms of panic in humans and escape in the UEEPM and suggest that the UEEPM may represent a paradigm to facilitate investigation into the neurochemical basis of extreme anxiety disorders.