Inhibition by antimanic drugs of hyperactivity induced by methamphetamine-chlordiazepoxide mixture in mice.
The effects of lithium chloride and other antimanic drugs on locomotor hyperactivity induced by a mixture of methamphetamine (MAMP) and chlordiazepoxide (CDZP) were examined in mice, using an Animex activity meter. CDZP (12.5 mg/kg) given SC in combination with MAMP (1 mg/kg) caused a marked increase in locomotor activity, as compared with that in mice treated with MAMP alone. However, when CDZP (12.5 mg/kg) was administered together with 0.5 or 2.0 mg/kg of MAMP, no significant enhancement was observed. Lithium (2 and 3 mEq/kg, IP) and carbamazepine (4 and 8 mg/kg, IP) inhibited the hyperactivity induced by the MAMP (1 mg/kg)-CDZP (12.5 mg/kg) mixture to the level of activity in animals treated with MAMP (1 mg/kg) alone. Lithium and carbamazepine alone at these doses caused no significant inhibition of locomotor activity in saline- or MAMP-treated mice. Haloperidol (0.1 mg/kg, IP) and chlorpromazine (0.5 mg/kg, IP) decreased the MAMP-CDZP mixture-induced hyperactivity without significantly inhibiting locomotor activity in the saline- or MAMP-treated group. However, haloperidol (0.2 mg/kg) and chlorpromazine (1 mg/kg) alone significantly inhibited locomotor activity in all of the saline-, MAMP- and MAMP-CDZP mixture-treated groups. These results indicate that antimanic drugs selectively inhibit the hyperactivity induced by the MAMP-CDZP mixture, but that neuroleptics are less selective in inhibiting the hyperactivity.
Okada
K
K
Department of Pharmacology, Okayama University Medical School, Japan.
Oishi
R
R
Saeki
K
K
D000818:Animals; D002220:Carbamazepine / Q000494:pharmacology*; D002707:Chlordiazepoxide / Q000037:antagonists & inhibitors*; D006948:Hyperkinesis / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D014149:Tranquilizing Agents / Q000494:pharmacology*
D014149:Tranquilizing Agents; D002220:Carbamazepine; D008694:Methamphetamine; D002707:Chlordiazepoxide