Involvement of the GABAA/benzodiazepine chloride ionophore receptor complex in the 5,7-DHT Induced anticonflict effect

Life Sci. 1991;49(2):139-53. doi: 10.1016/0024-3205(91)90027-9.

Abstract

The effects of drugs interacting with the GABAA/benzodiazepine chloride ionophore receptor complex (GABAA/BDZ-RC) on the anticonflict and biochemical effects observed after intracerebroventricular (i.c.v.) administration of 5,7-dihydroxytryptamine (5,7-DHT; 450 micrograms -14 days) were investigated in the rat using a modified Vogel's drinking conflict test. The GABAergic antagonistic drugs bicuculline, picrotoxin and Ro 15-4513 all counteracted the 5,7-DHT induced anxiolytic-like action in doses that did not alter the behavior per se, whereas flumazenil was ineffective in this respect. Also i.c.v. administration of 5-HT antagonized the 5,7-DHT induced anticonflict effect. Furthermore, 5,7-DHT-lesioned animals appeared more sensitive to the anticonflict effects of diazepam than sham-lesioned controls. The 5,7-DHT treatment produced marked depletions of 5-HT in the limbic system (80-90%) and hippocampus (90-95%), and an increase in the 5-HIAA/5-HT quotient in hippocampus. The effects on the levels of noradrenaline were comparatively small. The doses of bicuculline and picrotoxin antagonizing the 5,7-DHT induced anticonflict effect did not uniformly influence 5-HT levels or 5-HIAA/5-HT quotients. It is suggested that the anxiolytic-like effect observed in 5,7-DHT-lesioned rats in Vogel's drinking conflict test involves enhanced transmission at the GABAA/BDZ-RC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5,7-Dihydroxytryptamine / pharmacology*
  • Animals
  • Anti-Anxiety Agents*
  • Azides / pharmacology
  • Benzodiazepines / pharmacology
  • Bicuculline / pharmacology
  • Diazepam / pharmacology
  • Drinking Behavior / drug effects
  • Electroshock
  • Flumazenil / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Injections, Intraventricular
  • Limbic System / drug effects
  • Limbic System / metabolism
  • Male
  • Picrotoxin / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, GABA-A / physiology*
  • Serotonin / metabolism
  • Serotonin / pharmacology

Substances

  • Anti-Anxiety Agents
  • Azides
  • Receptors, GABA-A
  • Picrotoxin
  • Benzodiazepines
  • 5,7-Dihydroxytryptamine
  • Serotonin
  • Flumazenil
  • Ro 15-4513
  • Diazepam
  • Bicuculline