Ethopharmacological analysis of the open elevated plus-maze in mice

Exposure of rodents to an open elevated plus-maze (oEPM) elicits antinociception and increases plasma corticosterone levels. However, no studies have yet assessed the defensive behaviour repertoire of animals in this modified test. In Experiment 1, factor analysis was employed to characterise the behavioural profile of mice exposed to the oEPM. Experiments 2 and 3 assessed the effects of acute alprazolam (0.5–1.5 mg/kg; diazepam 0.5–1.5 mg/kg), pentylenetetrazole (10.0–30.0 mg/kg), yohimbine (2.0–6.0 mg/kg), mCPP (0.3–3.0 mg/kg), and acute and chronic fluoxetine (10.0–30.0 mg/kg) and imipramine (1.0–15.0 mg/kg) on behaviours identified in Experiment 1. The factor analyses revealed that behaviour in the oEPM can largely (77% total variance) be accounted for in terms of 3 factors: factor 1 (‘depth exploration’; e.g. head-dipping on the arms), factor 2 (‘cautious exploration of arms’; e.g. flatback approach), and factor 3 (‘risk assessment’; stretched attend postures – SAP). Experiments 2 and 3 showed that, over the dose range used, alprazolam selectively attenuated all measures of defensiveness. Similar, though more modest, effects were seen with diazepam. Confirming the intensity of the emotional response to the oEPM (nociceptive, endocrine and behavioural), relatively few significant behavioural changes were seen in response to the anxiogenic compounds tested. Although acute fluoxetine or imipramine treatment failed to modify behaviour in the oEPM, chronic fluoxetine (but not chronic imipramine) attenuated total flat back approach and increased head dipping outside the central square. Together, the results indicate that the oEPM induces behavioural defensive responses that are sensitive to alprazolam and chronic fluoxetine.

► Behavioural profile of mice exposed to the open elevated plus-maze (oEPM).
► Analysis revealed depth exploration, cautious exploration of arms and risk assessment.
► Acute fluoxetine or imipramine had no effects on defensive behaviour.
► Alprazolam, diazepam and chronic fluoxetine attenuated defensiveness.
► oEPM induces defensive behaviours that are sensitive to panicolytic-like drugs.