Effect of a protracted antidepressant treatment on signal transduction and [3H](-)-baclofen binding at GABAB receptors.
In membranes prepared from frontal cortex of rats receiving desmethylimipramine (10 mg/kg i.p. twice daily) or imipramine (7.5 mg/kg i.p. twice daily) for 3 weeks, the density of high-affinity gamma-aminobutyric acid (GABA)B recognition sites is increased when measured by [3H]GABA binding in the presence of an excess of bicuculline, but it is unchanged when measured by [3H](-)-baclofen binding. When the atypical antidepressant maprotiline was administered (10 mg/kg i.p. twice daily for 3 weeks), no change in the density of GABAB recognition sites was observed using either [3H]GABA or [3H](-)-baclofen as ligands. In addition, a protracted treatment with imipramine, desmethylimipramine and maprotiline failed to change GABAB receptor-coupled signal transduction as monitored by the ability of (-)-baclofen to inhibit the forskolin-stimulated adenylate cyclase activity in membranes prepared from frontal cortex and hippocampus or the cyclic AMP formation in slices from frontal cortex. Hence, after protracted antidepressant treatment, the increase of [3H]GABA binding may not reflect changes in the characteristics of the recognition sites of the GABAB receptors subclass coupled to the adenylate cyclase through a guanine nucleotide binding protein inhibitory (Ni).
Szekely
A M
AM
Fidia-Georgetown Institute for the Neurosciences, Georgetown University Medical Center, Washington, D.C.
Barbaccia
M L
ML
Costa
E
E
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D001418:Baclofen / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D003891:Desipramine / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D007099:Imipramine / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007700:Kinetics; D008297:Male; D008376:Maprotiline / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*
D000873:Anthracenes; D011963:Receptors, GABA-A; D005576:Colforsin; D008376:Maprotiline; D000262:Adenylyl Cyclases; D001418:Baclofen; D007099:Imipramine; D003891:Desipramine