Does the benzodiazepine antagonist Ro 15-1788 reverse the actions of picrotoxin and pentylenetetrazole on social and exploratory behaviour?

The effects of the benzodiazepine receptor antagonist, Ro 15-1788, were examined in combination with those of picrotoxin and pentylenetetrazole on social and exploratory behaviour in the rat. Both Ro 15-1788 (10 mg/kg) and picrotoxin (2 mg/kg) reduced social interaction, but there was no additive effect of these drugs together. Ro 15-1788 (10 and 20 mg/kg, which had no intrinsic effects in the holeboard alone) antagonized the reductions in exploratory head-dipping and motor activity produced by low (2 mg/kg), but not by high (4 mg/kg), doses of picrotoxin. In contrast, pentylenetetrazole (20 mg/kg) enhanced the reduction in social interaction produced by Ro 15-1788 (10 mg/kg), in accordance with previous findings that the reductions in spontaneous behaviour in the holeboard produced by pentylenetetrazole are enhanced by Ro 15-1788. These results show that there are clear functional interactions between these two compounds at the GABA-benzodiazepine receptor complex in the CNS, and that the nature of these interactions differs for picrotoxin and pentylenetetrazole.