This study investigates the effects of
benzodiazepine receptor inverse agonists on the locomotor and exploratory behaviour of mice when tested in a familiar environment. The weak partial inverse agonist
Ro 15-3505 (0.3, 1, 3 mg/kg i.p.) significantly increased locomotion and hole-dipping in habituated mice. However, the more efficacious partial inverse agonists
Ro 15-4513 (0.3, 1, 3 mg/kg i.p.) and
Ro 19-4603 (0.03, 0.1, 0.3 mg/kg i.p.) had no effect on these parameters. The
benzodiazepine receptor antagonist
flumazenil (3, 10, 20 mg/kg i.p.) also increased locomotion and hole-dipping in habituated mice, although like
Ro 15-3505, these effects were of short duration occurring largely in the first 15 min following injection. Opposite effects were obtained with the partial
benzodiazepine agonist
Ro 17-1812 (1, 3, 10 mg/kg i.p.) which produced a longer-lasting significant decrease in hole-dipping behaviour in habituated mice without altering locomotion. Finally, in contrast to its effects in habituated animals,
Ro 15-3505 (0.3, 1, 3 mg/kg i.p.) did not modify either locomotion or exploration in mice which were tested in a novel environment, showing that the effects of the inverse agonist were state-dependent. This demonstration that, under certain conditions, the weak
benzodiazepine receptor inverse agonist
Ro 15-3505 and the antagonist
flumazenil, produce behavioural activation is in accordance with the work of others suggesting that these classes of compound may increase arousal and may therefore be of some value in treatment of
memory disorders.