Reversal of the anti-conflict action of valproate by various GABA and benzodiazepine antagonists

Life Sci. 1984 Jun 18;34(25):2525-33. doi: 10.1016/0024-3205(84)90290-x.

Abstract

The effects of RO 15-1788, RO 5-3663, picrotoxin and bicuculline on the anti-conflict properties of valproate were studied in rats using a modified Vogel 's conflict test procedure. A low dose of the benzodiazepine (BDZ) antagonist, RO 15-1788 (5 mg/kg), blocked the anti-punishment properties of valproate (400 mg/kg), whereas no antagonism was observed after a high dose (25 mg/kg) of the BDZ antagonist. High doses of RO 5-3663 or picrotoxin also reversed the anti-conflict action of valproate. Bicuculline did not change the effects of valproate in this test situation. The suppressive effect of valproate on locomotor activity was reversed by a low dose (5 mg/kg) of RO 15-1788, but not by the other antagonists. RO 5-3663 was the only antagonist which effectively reversed the muscle relaxant effects of valproate observed in a Rotarod performance test. These findings indicate that various pharmacological actions of valproate may be due to a complex interplay with several sites at the GABA-BDZ-receptor complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzodiazepines / antagonists & inhibitors*
  • Benzodiazepinones / pharmacology
  • Bicuculline / pharmacology
  • Conflict, Psychological*
  • Flumazenil
  • GABA Antagonists*
  • Male
  • Motor Activity / drug effects
  • Picrotoxin / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Cell Surface / drug effects
  • Receptors, GABA-A
  • Valproic Acid / pharmacology*

Substances

  • Benzodiazepinones
  • GABA Antagonists
  • Receptors, Cell Surface
  • Receptors, GABA-A
  • Picrotoxin
  • Benzodiazepines
  • Flumazenil
  • Valproic Acid
  • Ro 5-3663
  • Bicuculline