5-HT1A-sensitive adenylyl cyclase of rodent hippocampal neurons: effects of antidepressant treatments and chronic stimulation with agonists.
The effects of chronic treatment with desimipramine (a tricyclic antidepressant), fluoxetine [a specific 5-hydroxytryptamine (5-HT) uptake inhibitor], clorgyline (a specific monoamine oxydase inhibitor of A type), ipsapirone (a specific 5-HT1A receptor agonist) as well as electroconvulsive shock treatment were investigated on rat hippocampal 5-HT1A receptors negatively coupled to adenylyl cyclase. Drugs were injected intraperitoneally in rats for 2 or 3 weeks, and biochemical determinations were made 4 to 72 hr after the final dose. Chronic treatments with desimipramine, ipsapirone and fluoxetine did not induce any change in the 5-HT1A-induced inhibition of the adenylyl cyclase activity. In contrast, chronic treatment with clorgyline and electroconvulsive shock treatment induced a slight but significant reduction of 5-HT's ability to inhibit hippocampal adenylyl cyclase. This indicates that, at least in hippocampal neurons, the 5-HT1A receptor coupled to adenylyl cyclase is not easily desensitized. This was verified in vitro on murine hippocampal neurons in culture, by measuring the effects of intense stimulation (1 and 2 hours), with 5-HT, ipsapirone and 8-hydroxy-2-(di-n-propylamino)tetralin. Indeed, such stimulations did not significantly affect the 5-HT1A receptor-induced inhibition of cAMP production in these hippocampal neurons in culture. Our results indicate that it is not the post-synaptic 5-HT1A receptor of hippocampus that is modified during antidepressant treatments, at least at the level of its coupling to adenylyl cyclase.
Varrault
A
A
Centre National de la Recherche Scientifique-Institut National de la Santé et de la Recherche Medicale de Pharmacologie-Endocrinologie, Montpellier, France.
Leviel
V
V
Bockaert
J
J
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003010:Clorgyline / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000201:enzymology* / Q000502:physiology; D007213:Indomethacin / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D011743:Pyrimidines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*
D000067956:Adenylyl Cyclase Inhibitors; D000928:Antidepressive Agents; D011743:Pyrimidines; D011985:Receptors, Serotonin; D005473:Fluoxetine; C034674:5-hydroxyindomethacin; D012701:Serotonin; C043077:ipsapirone; D003010:Clorgyline; D007213:Indomethacin