Benzodiazepine inverse agonist FG-7142-induced delayed behavioral depression in mice

Effect of acute administration of a benzodiazepine-inverse agonist, FG-7142, on forced swimming-induced depression was investigated in mice. A single injection of FG-7142 (40 mg/kg) showed a delayed increase in behavioral despair, the peak effect being observed on the 5th and 6th day of FG-7142 administration. beta-Adrenoceptor agonist isoprenaline significantly potentiated FG-7142-induced behavioral despair. FG-7142-induced depression was sensitive to reversal by chronic treatment with propranolol or desipramine. These observations suggest that the inverse agonist FG-7142 upregulates beta-adrenoceptor population leading to behavioral despair in mice.