The 5,7-DHT-induced anticonflict effect is dependent on intact adrenocortical function.
We have recently reported that the anxiolytic-like effect observed in rats severely depleted of brain serotonin (5-HT) by means of 5,7-DHT is indirect and probably involves the GABA(A)/benzodiazepine chloride ionophore receptor complex (GABAA/BDZ-RC). One tentative explanation for this effect considered the involvement of corticosteroids. In the present series of experiments we have therefore investigated the effect of adrenalectomy (ADX) on the 5,7-DHT-induced anxiolytic-like effect displayed by rats in Vogel's conflict test. ADX totally abolished the anticonflict effect of the 5,7-DHT lesion. Replacement treatment with corticosterone, but not with dexamethasone, reinstated the anticonflict effect. These results indicate that an intact adrenocortical function, possibly via brain steroid type I receptors, is required for the expression of the 5,7-DHT-induced anxiolytic-like effect. It is postulated that ADX lowers the concentration of endogenous positive modulators at the GABAA/BDZ-RC to a level no longer sufficient to produce anxiolytic-like effects in 5,7-DHT-lesioned animals. The finding that 5,7-DHT-lesioned animals were more sensitive than sham-lesioned controls to the anticonflict effect of the barbiturate-like corticosteroid THDOC provides further support for the contention that an increased endogenous activity at the GABAA/BDZ-RCes is involved in the anxiolytic-like effect observed in rats with a severe depletion of brain 5-HT.
Söderpalm
B
B
Department of Pharmacology, University of Göteborg, Sweden.
Engel
J A
JA
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000302:Adrenal Cortex / Q000187:drug effects / Q000502:physiology*; D000315:Adrenalectomy; D000818:Animals; D003220:Conflict, Psychological; D003345:Corticosterone / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D004597:Electroshock; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012684:Sensory Thresholds / Q000187:drug effects
D015116:5,7-Dihydroxytryptamine; D003900:Desoxycorticosterone; C009413:tetrahydrodeoxycorticosterone; D003907:Dexamethasone; D003345:Corticosterone