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  • Title: Effect of a protracted antidepressant treatment on signal transduction and [3H](-)-baclofen binding at GABAB receptors.
    Author: Szekely AM, Barbaccia ML, Costa E.
    Journal: J Pharmacol Exp Ther; 1987 Oct; 243(1):155-9. PubMed ID: 2822895.
    Abstract:
    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).
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