EFFECT OF THE 5-HT2 ANTAGONIST KETANSERIN ON SALT APPETITE IN THE RAT

The 5-HT2 antagonist ketanserin inhibited salt appetite induced by subchronic deoxycorticosterone acetate (DOCA) treatment, as well as salt appetite induced by sodium depletion (which is governed by the synergy of aldosterone and angiotensin in the brain). The effect of ketanserin was more evident following intraperitoneal than intracerebroventricular injection. On the other hand, ketanserin did not inhibit either salt intake induced by intracranial renin injection, or the need-free salt intake of the multidepleted female rat, which is not dependent on the renin-angiotensin-aldosterone system. These findings suggest that the antinatriorexic action of ketanserin is selective for the mineralcorticoid mechanisms controlling salt appetite. Ritanserin, too, a potent 5-HT, antagonist showing a different receptor selectivity profile from that of ketanserin, suppressed DOCA-induced salt appetite, thus supporting the involvement of 5-HT receptors in the antinatriorexic action. DOCA treatment alters serotonin metabolism in the central nervous system and it has been proposed that changes in 5-HT metabolism may be important in the genesis of DOCA-induced hypertension. The present results indicate that ketanserin inhibits DOCA-induced salt appetite and suggest that serotoninergic mechanisms might be involved in the elicitation of mineral-ocorticoid-induced salt appetite.