Anatomical and physiological relationships between central serotonin and vasopressin

Abstract

The role of serotonin (51M in the physiological regulation of AVP secretion is controversial. Neuroanatomical studies, largely in rats but also in human brains, have suggested that 5HT may have a direct modulatory effect on magnocellular vasopressin (AVP) secretion. Pharmacological and neurophysiological studies in animals have provided further evidence to support this and suggest that increase in 5HT neurotransmission leads to a rise in plasma AVP and that 5HT may be important in osmoregulated AVP secretion Studies investigating the importance of 511T as a modulator of AVP release in humans have not be undertaken. Indirect evidence of a putative role derives from the occurrence of hyponatraemia, and possible inappropriate AVP secretion,associated with the clinical use of drugs, particularly antidepressants, which have effects on 5HT neurotransmission. In addition there has been some suggestion that AVP secretion may be abnormal in depression where there is a putative abnormality of the 5HT nervous system. This research has approached the study of anatomical and physiological relationships between 5HT and AVP in 3 ways. Firstly through studies in normal man, secondly by studies in depressed patients, as a putative disease model of 5HT neurotransmission, and thirdly to more extensively explore the effect of pharmacological manipulation of 5HT neurotransmission using an animal model of osmoregulation. Studies in man found no evidence that 7 days treatment with a 5HT reuptake inhibitor (Fluoxetine) had a significant effect on osmoregulated AVP secretion. Studies in elderly depressed patients showed that there was an apparent deficiency of osmoregulated AVP secretion with normal ageing but found no evidence that either moderate depressive il lness, or treatment of the depression with Fluoxetine, had significant effect on water balance. Studies in the rat model of osmoregulation showed that acute 5HT reuptake inhibition stimulated basal AVP secretion and increased the osmotic sensitivity of AVP secretion but had no effect on the osmotic threshold of secretion. Chronic treatment (21 days) with the reuptake inhibitor had no significant effect on basal AVP secretion or on the osmotic threshold but significantly decreased the osmotic sensitivity of AVP secretion. Studies with the 5HT2/5HTIc antagonist, Ritanserin, and the 5HT2 agonist, DOI, suggested that this modulatory effect was not mediated through these receptor subtypes. Autoradiographic studies identified a low density of 5HT2 and 5HTIa receptors in the vicinity of the magnocellular neurons of the rat hypothalamus. The results suggested that 5HT modulates AVP secretion indirectly, possibly by inhibition of inhibitory afferent stimuli. This is of little physiological consequencien the normal rat and probably in healthy man where there is rapid accommodation and autoregulation. In situations where there is a dysfunction of the normal adaptive mechanisms such as in depression,the role of 5HT may be more important and occasionally may lead to severe hyponatraemia.