Vasopressin, oxytocin, corticotrophin-releasing factor, and sodium responses during fluoxetine administration in the rat

Abstract

Hyponatremia has been observed in elderly patients treated with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. The pathogenesis of this effect is not known, but enhanced release of vasopressin (VP) and its renal actions may be a possible mechanism. Excess secretion of VP in combination with large fluid intake is known to induce hyponatremia. We determine if chronic fluoxetine administration in association with liberal fluid intake will induce hyponatremia via enhanced release of VP. We used a previously described model in which fluid intake is forced by administering rats a nutritionally balanced liquid diet. Male Sprague-Dawley rats in groups of 10 were randomized to solid and liquid diets, and each diet group administered daily i.p. injections of fluoxetine (10 mg/kg) or saline for 10 d. Water was given ad libitum to all groups. Daily weight, fluid and food intake, and urine output were measured. On d 10, rats were killed by rapid guillotine decapitation 1-3 h after injection. Trunk blood was collected for measurements of plasma VP and oxytocin (OT) and serum sodium (Na), BUN, creatinine, and glucose. Pituitary glands were assayed for VP and OT content. VP mRNA in the paraventricular and supraoptic nuclei (PVN and SON) and corticotrophin-releasing factor (CRF) mRNA in the PVN were measured by in situ hybridization histochemistry. Fluid intake was significantly higher in groups maintained on liquid vs solid diet (p < 0.0001), as was urine output (p < 0.0001). Fluoxetine-treated rats gained significantly less weight than placebo-treated rats (p = 0.01), in keeping with fluoxetine's anorexigenic properties. However, no significant differences were found among the groups in Na, plasma VP or OT, pituitary VP or OT, or PVN CRF or VP mRNA levels. We conclude that administration of fluoxetine to laboratory rats in the dose and duration used in this study does not significantly affect hypothalamic expression, pituitary stores, or peripheral secretion of VP.