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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.

Rationale and Objectives: The unstable elevated exposed plus maze (UEEPM) has been proposed as a novel model of anxiety which elicits unconditioned escape-related behaviour in rats thought to mimic the persistent "fight/flight" state exhibited by patients suffering from extreme anxiety disorders. This study investigated the predictive validity of the UEEPM by examining the behaviour of rats exposed to the test following administration of drugs known to induce panic and anxiety in panic disorder and post-traumatic stress disorder patients, namely m-chlorophenylpiperazine (mCPP), caffeine and yohimbine. The sensitivity of the UEEPM to two further putative anxiogenic agents, the benzodiazepine partial inverse agonist FG 7142 and pentylenetetrazole (PTZ), was also assessed., Methods: Male Hooded Lister rats received a single dose of mCPP (0.5-2.0 mg/kg; ip), caffeine (3.0-30.0 mg/kg; ip), yohimbine (1.25-5.0 mg/kg; ip), FG 7142 (3.0-30.0 mg/kg; ip) or PTZ (3.0-30.0 mg/kg; ip) before being exposed to the UEEPM for a period of 5 min. Subjects' behaviour was analysed to determine the effects of each compound on unconditioned escape., Results: mCPP (1.0 and 2.0 mg/kg), caffeine (30 mg/kg), FG 7142 (3.0 and 30.0 mg/kg) and PTZ (30.0 mg/kg) significantly increased animals' propensity to escape from the UEEPM, i.e. they had a clear anxiogenic effect, whilst yohimbine had no effect on escape., Conclusions: The UEEPM is sensitive to the behavioural effects of anxiogenic agents. Furthermore, pharmacological similarities exist between symptoms of panic and anxiety in patients and escape from the UEEPM in rats. The UEEPM may therefore represent a paradigm to facilitate investigation into the neurochemical basis of extreme anxiety disorders.