Effect of third ventricle administration of L-694,247, a selective 5-HT1D receptor agonist, on water intake in rats

L-694,247, a selective 5-HT1D receptor agonist, injected directly into the third ventricle (2.5, 5.0, and 10.0 micrograms/rat) of dehydrated rats induced a dose-dependent partial blockade of water intake. Injected in this way, the compound abolishes drinking behavior induced by third ventricle administration of carbachol (2 micrograms/rat), angiotensin II (5 ng/rat), and isoproterenol (40 micrograms/rat). In addition, intraventricular injections of L-694,247 did not modify water intake in normohydrated rats. The effects of L-694,247 are due to a specific interaction with 5-HT1D receptors, because its inhibitory effect on water intake in dehydrated rats is blocked by the previous administration of a 5-HT1D antagonist, GR 127935 (5 micrograms/rat), directly into the third ventricle. It is concluded that central 5-HT1D receptor activation disrupts the functional integrity of central pathways related to drinking behavior.