Fluoxetine-induced presser response in freely moving rats: a role for vasopressin and sympathetic tone

The present study was performed in order to assess, in freely moving rats, the cardiovascular effects of central administration of fluoxetine, a serot onin reuptake inhibitor. Two kinds of experiments were performed: 1) acute central administration of fluoxetine, and 2) chronic intraperitoneal admini stration of fluoxetine plus selegiline, a monoamine oxidase B inhibitor. In tracerebroventricular (i.c.v.) administration of fluoxetine (5-50 mug) indu ced an increase in brood pressure. This fluoxetine-induced presser response reached its maximal 1 hour after injection without any significant change in heart rate. At the dose of 10 mug i.c.v., fluoxetine significantly incre ased mean brood pressure by 16 +/- 4 mmHg. This presser response was reduce d by an intravenous (i.v.) pretreatment with the alpha (1)-adrenoceptor ant agonist, prazosin (500 mug kg(-1)) (+ 7 +/- 4 mmHg; P < 0.05) or with the V -1A-vasopressin receptor antagonist (20 <mu>g kg-1) (+ 5 +/- 3 mmHg, P < 0. 05). The presser response was completely abolished by a concomitant pretrea tment with prazosin plus the V1A-vasopressin receptor antagonist. Pretreatm ent with the <beta>-adrenoceptor antagonist, propranolol (1 mg kg(-1) i.v.) , or the 5-HT2 receptor antagonist, ketanserine (5 mg kg(-1) i.v.), did not modify the fluoxetine-induced presser response. In freely moving rats rece iving fluoxetine (10 mug i.c.v.), vasopressin plasma levels were significan tly higher (39 +/- 5 pg mL(-1)) than in rats receiving 10 muL i.c.v. saline (14 +/- 4 pg mL(-1)). A 30 day intraperitoneal (i.p.) administration of fl uoxetine in association with selegiline induced an increase in noradrenalin e plasma levels and locomotor activity without any significant change in bl ood pressure and heart rate. These data suggest that, the presser response elicited by central acute administration of fluoxetine is mediated by both an increase in sympathetic tone and vasopressin release. This observation c ould suggest the putative interest of alpha (1)-adrenoceptor and/or V-1A-va sopressin receptor antagonists in the treatment of "Serotonin Syndrome". (( C)) 2000 Editions scientifiques et medicales Elsevier SAS.