THE EFFECT OF ACUTE PHARMACOLOGICAL MANIPULATION OF CENTRAL SEROTONINNEUROTRANSMISSION ON OSMOREGULATED SECRETION OF ARGININE-VASOPRESSIN IN THE RAT

To explore the hypothesis that serotonin (5-HT) is important in osmore gulated arginine vasopressin (AVP) secretion, we administered (i.p.) f luoxetine (FL) a 5-HT reuptake inhibitor (10 mg/kg body weight), ritan serin (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 hy drochloride (DOI), a 5-HT2 receptor agonist (1 mg/kg body weight) or v ehicle to rats 30 min before they were given an osmotic challenge. Rat s received distilled water, normotonic saline (150 mmol NaCl/l) or hyp ertonic 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) effe cts on plasma osmolality and plasma sodium but FL, RIT and DOI did not have any significant effect on this stimulus. FL had no significant e ffect on the osmotic threshold of AVP release but significantly (P<0.0 01) 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 sign ificant 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 sign ificant effect on the AVP response to plasma osmolality and did not si gnificantly alter the FL-augmented AVP response, suggesting that neith er 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 b ut that the mechanism of this is unknown and is apparently not through the 5-HT2 or 5-HT1c receptor subtypes.