Involvement of the GABAA/benzodiazepine chloride ionophore receptor complex in the 5,7-DHT Induced anticonflict effect.
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.
Department of Pharmacology, University of Göteborg, Sweden.
B
B
Söderpalm
J A
JA
Engel
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents; D001386:Azides / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004327:Drinking Behavior / Q000187:drug effects; D004597:Electroshock; D005442:Flumazenil / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology
D015116:5,7-Dihydroxytryptamine; D014151:Anti-Anxiety Agents; D001386:Azides; D001569:Benzodiazepines; D001640:Bicuculline; D003975:Diazepam; D005442:Flumazenil; D010852:Picrotoxin; D011963:Receptors, GABA-A; D012701:Serotonin; C042957:Ro 15-4513