The effect of Ro 15-4513,an inverse agonist at the benzodiazepine receptor,on the exploratory response to novelty in the playground maze

The effects of chlordiazepoxide and the inverse agonist, Ro 15-4513, were compared on the exploratory response of rats to a novel object introduced into a familiar environment containing seven familiar objects. While chlordiazepoxide (5 mg/kg) increased the novelty response, Ro 15-4513 reduced the response in a dose-dependent manner (0.5-5.0 mg/kg). This action was specific to novelty since the response to the familiar objects was unaffected. Both drugs produced some reduction in ambulation. The effects of both drugs were blocked by flumazenil (10 mg/kg), which at this dose did not itself have any intrinsic effect on the response. Muscimol (0.001 mg/kg) had a weak chlordiazepoxide-like effect and baclofen (3 mg/kg) had a weak effect in the opposite direction.