Ethopharmacological analysis of the unstable elevated exposed plus maze, a novel model of extreme anxiety: predictive validity and sensitivity to anxiogenic agents.
OBJECTIVE
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.
Jones
Nicholas
N
Department of Psychology, University College London, Gower Street, WC1E 6BT, UK. nick@psychol.ucl.ac.uk
Duxon
Mark S
MS
King
Sheila M
SM
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D002110:Caffeine / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology; D005069:Evaluation Studies as Topic; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D010433:Pentylenetetrazole / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D002243:Carbolines; D000697:Central Nervous System Stimulants; D018756:GABA Antagonists; D010879:Piperazines; D017366:Serotonin Receptor Agonists; D015016:Yohimbine; D002110:Caffeine; C035874:FG 7142; C015068:1-(3-chlorophenyl)piperazine; D010433:Pentylenetetrazole