Changesin5-HT1AreceptorbindingandG-protein：在结合与G蛋白5-HT1A受体的变化.pdfVIP

Research Paper Article de recherche Changes in 5-HT1A receptor binding and G-protein activation in the rat brain after estrogen treatment: comparison with tamoxifen and raloxifene Maryvonne Le Saux, MSc; Thérèse Di Paolo, PhD Molecular Endocrinology and Oncology Research Center, and Faculté de pharmacie, Université Laval, Québec, Que. 2003 CCNP Heinz Lehmann Award Paper Objective: It is thought that an imbalance in serotonergic neurotransmission may underlie many affective disorders. Thus, the serotonin- 1A (5-HT1A) receptor is a target for antidepressant and neuroleptic drugs. It has been reported that estrogens modulate serotonergic neu- rotransmission. Therefore, we investigated the effect of long-term ovariectomy on 5-HT1A receptor–specific binding and G-protein activa- tion in the brain. Correction therapy with estradiol was compared with treatments using the selective estrogen receptor modulators tamoxifen and raloxifene. Methods: Four months after ovariectomy, Sprague–Dawley rats were treated with vehicle, 17β-estradiol (80 µg/kg), tamoxifen (1 mg/kg) or raloxifene (1 mg/kg) subcutaneously for 2 weeks. Specific binding to 5-HT1A receptors was assessed 3 by autoradiography of brain sections using the 5-HT1A agonist [ H]8-OH-DPAT. 5-HT1A receptor stimulation was measured using R-(+)-8- OH-DPAT-stimulated [35S]GTPγS-binding autoradiography. Results: Ovariectomy decreased uterine weight, which was corrected by 3 estradiol; tamoxifen and raloxifene parti