The hypothermic effects of intraperitoneal (IP) administration of the full
benzodiazepine agonist
loprazolam (1, 10 mg/kg); the partial agonist
Ro 17-1812 (1, 10 mg/kg); the
benzodiazepine receptor antagonist
flumazenil (10, 20 mg/kg); the
benzodiazepine inverse agonists
Ro 15-4513 (1, 3, 10 mg/kg) and
Ro 19-4603 (0.03, 0.1, 0.3 mg/kg) and the
beta-carboline inverse agonists
FG 7142 (10, 30 mg/kg) and
DMCM (1, 3, 10 mg/kg) were investigated in three strains of mice. TO mice were less sensitive than CBA/cA and DBA/2 mice, since only
loprazolam and the partial and full
beta-carboline inverse agonists
FG 7142 and
DMCM lowered body temperature in these animals. CBA/cA mice were particularly sensitive to the hypothermic effects of
loprazolam and
Ro 17-1812, and also responded to the
beta-carboline but not the benzo diazepine inverse agonists. In contrast, DBA/2 mice responded with moderate
hypothermia to
loprazolam,
Ro 17-1812, and to the partial inverse agonist
Ro 15-4513, and exhibited marked
hypothermia in response to the more efficacious
benzodiazepine inverse agonist
Ro 19-4603 and to
FG 7142 and
DMCM.
Flumazenil did not alter body temperature. DBA/2 mice were also more sensitive to the
convulsant activity of inverse agonists than TO mice. CBA/cA mice exhibited enhanced sensitivity to the
convulsant, but not the hypothermic, effects of
Ro 19-4603, showing dissociation of these responses. The mechanisms underlying the genetic differences in sensitivity of mice to the hypothermic and
convulsant action of the different
ligands are unknown and warrant further investigation.