Fluoxetine-induced pressor 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 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 microg) 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 microg 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 alpha1-adrenoceptor antagonist, prazosin (500 microg kg(-1)) (+ 7 +/- 4 mmHg, P <0.05) or with the V1A-vasopressin receptor antagonist (20 microg 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 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 pressor response. In freely moving rats receiving fluoxetine (10 microg i.c.v.), vasopressin plasma levels were significantly higher (39 +/- 5 pg mL(-1) than in rats receiving 10 microL 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 alpha1-adrenoceptor and or V1A-vasopressin receptor antagonists in the treatment of "Serotonin Syndrome".
Lazartigues
E
E
Laboratoire de Pharmacologie Médicale et Clinique, Inserm U317 and Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, Faculté de Médecine, Toulouse, France.
Brefel-Courbon
C
C
Bagheri
H
H
Costes
S
S
Gharib
C
C
Tran
M A
MA
Senard
J M
JM
Montastruc
J L
JL
D000704:Analysis of Variance; D000818:Animals; D004347:Drug Interactions; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D014667:Vasopressins / Q000502:physiology*
D005473:Fluoxetine; D018696:Neuroprotective Agents; D012642:Selegiline; D017367:Selective Serotonin Reuptake Inhibitors; D014667:Vasopressins