Fluoxetine‐induced pressor response in freely moving rats: a role for vasopressin and sympathetic tone

Abstract— The present study was performed in order to assess, in freely moving rats, the cardiovascular effects of central administration of fluoxetine, a serotonin reuptake inhibitor. Two kinds of experiments were performed: 1) acute central administration of fluoxetine, and 2) chronic intraperitoneal administration of fluoxetine plus selegiline, a monoamine oxidase B inhibitor. Intracerebroventricular (i.c.v.) administration of fluoxetine (5–50 μg) induced an increase in blood pressure. This fluoxetine‐induced pressor response reached its maximal 1 hour after injection without any significant change in heart rate. At the dose of 10 μg i.c.v., fluoxetine significantly increased mean blood pressure by 16 ± 4 mmHg. This pressor response was reduced by an intravenous (i.v.) pretreatment with the α1‐adrenoceptor antagonist, prazosin (500 μg kg−1) (+ 7 ± 4 mmHg, P < 0.05) or with the V1A‐vasopressin receptor antagonist (20 μg kg−1) (+ 5 ± 3 mmHg, P < 0.05). The pressor response was completely abolished by a concomitant pretreatment with prazosin plus the V1A‐vasopressin receptor antagonist. Pretreatment with the β‐adrenoceptor antagonist, propranolol (1 mg kg−1i.v.), or the 5‐HT2 receptor antagonist, ketanserine (5 mg kg−1i.v.), did not modify the fluoxetine‐induced pressor response. In freely moving rats receiving fluoxetine (10 μg i.c.v.), vasopressin plasma levels were significantly higher (39 ± 5 pg mL−1) than in rats receiving 10 μL i.c.v. saline (14 ± 4 pg mL−1). A 30 day intraperitoneal (i.p.) administration of fluoxetine in association with selegiline induced an increase in noradrenaline plasma levels and locomotor activity without any significant change in blood pressure and heart rate. These data suggest that, the pressor response elicited by central acute administration of fluoxetine is mediated by both an increase in sympathetic tone and vasopressin release. This observation could suggest the putative interest of α1‐adrenoceptor and/or V1A‐vasopressin receptor antagonists in the treatment of “Serotonin Syndrome”.