Intracerebroventricular 5,7-DHT alters the in vitro function of rat cortical GABAA/benzodiazepine chloride ionophore receptor complexes.
We have earlier presented data indicating that the anxiolytic-like effect obtained in rats after depletion of brain 5-HT by means of PCPA or 5,7-DHT treatment is indirect and appears to involve the GABAA/benzodiazepine chloride ionophore receptor complex (GABAA/BDZ-RC), and that it is abolished by adrenalectomy. In the present series of experiments we have therefore investigated the 36Cl(-)-uptake in rat synaptoneurosomal preparations of central cortices from 5,7-DHT- and SHAM-lesioned animals. The GABA as well as the 3 alpha,5 alpha-tetrahydrodeoxycorticosterone (THDOC) induced picrotoxin-sensitive increase in 36Cl(-)-uptake was significantly lower than that observed in the SHAM-lesioned animals, indicating that the 5,7-DHT lesion has rendered the GABAA/BDZ-RC subsensitive to two of its tentative endogenous ligands. This effect of the 5,7-DHT lesion on the function on the GABAA/BDZ-RC was reversed by adrenalectomy, indicating that an intact adrenocortical function is required for the development of GABAA/BDZ-RC subsensitivity in 5,7-DHT-lesioned rats. A tentative conclusion of these findings is that the 5,7-DHT lesion induces an increase in release of GABA and/or barbiturate-like steroids and that this increase is reversed by adrenalectomy. The findings from these in vitro studies parallel those from our previous behavioral experiments and provide further support for the notion that a decreased serotonergic influence in the central nervous system may, possibly via the adrenocortical system, enhance the function of the GABAA/BDZ-RC.
Söderpalm
B
B
Department of Pharmacology, University of Göteborg, Sweden.
Andersson
G
G
Johannessen
K
K
Engel
J A
JA
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000315:Adrenalectomy; D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002552:Cerebral Ventricles; D002713:Chlorine; D066298:In Vitro Techniques; D008297:Male; D011868:Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D011868:Radioisotopes; D011963:Receptors, GABA-A; D015116:5,7-Dihydroxytryptamine; D002713:Chlorine