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Donatella Marazziti, Giorgio Consoli, Francesca Golia, Stefano Baroni, Irene Masala, Marina Carlini, Mario Catena Dell’OssoDipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, Pisa, ItalyAbstract: Trazodone is an antidepressant which behaves as a selective 5-HT2 antagonist and 5-HT reuptake inhibitor. The lack of information on its effects in vivo prompted us to evaluate α2-adrenoceptors by means of the specific binding of [3H]-rauwolscine, and the 5-HT transporter (SERT) by means of the binding of [3H]-paroxetine ([3H]-Par), in platelets of depressed patients, before and after one month of treatment with trazodone (75–300 mg/day). Twenty-five outpatients of both sexes with a diagnosis of major depression, as assessed by the Structured Clinical Interview for DSM IV, were included in the study. Depressive symptoms were evaluated by means of the Hamilton Rating Scale for Depression: the total score (mean ± SD) was 20 ± 6 at baseline (t0) and 7 ± 4 after one month of treatment (t1). Platelet membranes, [3H]-rauwolscine and [3H]-Par bindings were carried out according to standardized protocols. The results showed that the Bmax values of [3H]-Par were statistically lower at t1 than at t0 (733 ± 30 vs 1471 ± 99, P < 0.001), while the Kd and the [3H]-rauwolscine binding parameters remained unchanged. The findings of this study suggest that in vivo trazodone modifies the number of the SERT proteins and that, perhaps, most of its antidepressant properties are related to this activity.Keywords: trazodone, depression, serotonin, platelets, α2-adrenoreceptors, [3H]-rauwolscine, serotonin transporter, [3H]-paroxetine

D Marazziti,S Baroni, L Palego,I Masala,G Consoli, M Catena Dell’Osso,G Giannaccini, A LucacchiniDipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università di Pisa, Pisa, ItalyAbstract: Although the main biological hypothesis on the pathophysiology of obsessive-compulsive disorder (OCD) is centered on the serotonin system, indications are available that other neurotransmitters, and even second messengers, particularly the cyclic adenosine monophosphate (cAMP) signaling, may be involved, though effective data are few. Therefore, the aim of the present study was to evaluate and compare the basal and isoprenaline (ISO)-stimulated velocity of adenylate-cyclase (AC) in human platelet membranes of patients with OCD and healthy control subjects. The results showed that the basal and ISO-stimulated AC activity, as well as the dose-response curves of ISO by using agonist concentrations ranging between 0.1 nM and 10 µM, were not different in the two groups. However, OCD patients showed lower EC50 and higher Emax values than healthy subjects. These findings suggest the presence of supersensitive β-adrenergic receptors in platelets of OCD patients.Keywords: obsessive-compulsive disorder, norepinephrine, second messengers, adenylate-cyclase, platelets, isoprenaline, β-adrenergic receptors