The effect of acute pharmacological manipulation of central serotonin neurotransmission on osmoregulated secretion of arginine vasopressin in the rat

Abstract

ABSTRACT To explore the hypothesis that serotonin (5-HT) is important in osmoregulated arginine vasopressin (AVP) secretion, we administered (i.p.) fluoxetine (FL) a 5-HT reuptake inhibitor (10 mg/kg body weight), ritanserin (RIT), an antagonist at the 5-HT2 and 5-HT1c receptor subtypes (1 mg/kg body weight), 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI), a 5-HT2 receptor agonist (1 mg/kg body weight) or vehicle to rats 30 min before they were given an osmotic challenge. Rats received distilled water, normotonic saline (150 mmol NaCl/l) or hypertonic saline (500 mmol NaCl/l) (20 ml/kg i.p) and were killed 30 min later. The osmotic stimulus alone produced significant (P<0·001) effects on plasma osmolality and plasma sodium but FL, RIT and DOI did not have any significant effect on this stimulus. FL had no significant effect on the osmotic threshold of AVP release but significantly (P<0·001) increased basal AVP secretion from 1·6 ± 1·0 to 3·1 ± 1·3 (s.e.m.) pmol AVP/l and significantly (P<0·001) increased the AVP response to changes in plasma osmolality: vehicle-treated, 0·7 ± 0·4; FL-treated, 1·7 ± 0·2 pmol AVP/l per mOsm per kg. Neither RIT nor DOI had any significant effect on basal or stimulated AVP secretion. In a second study, RIT was administered 60 min i.p. prior to FL i.p. (doses as above), which was followed 30 min later by a hypertonic stimulus i.p. and rats were killed 30 min after hypertonic saline treatment. RIT had no significant effect on the AVP response to plasma osmolality and did not significantly alter the FL-augmented AVP response, suggesting that neither the 5-HT2 nor the 5-HT1c receptors are involved in the response of AVP to FL. We conclude that FL modulates osmoregulated AVP secretion but that the mechanism of this is unknown and is apparently not through the 5-HT2 or 5-HT1c receptor subtypes. Journal of Endocrinology (1993) 139, 77–87