Effects of d-fenfluramine, MK-212, and ondansetron on saline drinking in two-choice tests in the rehydrating rat.

The aim of the present studies was to investigate the effects of serotonergic compounds on preference for isotonic saline and aversion to hypertonic saline, respectively. Twenty-two-hour water-deprived rats were divided into two groups: The first was given a choice between 0.9% saline and water in a 30-min test; the second was given a choice between 1.8% saline and water. Animals were tested following administration of d-fenfluramine, the 5-HT1C receptor agonist 6-chloro-2-(1-piperazinyl)pyrazine (MK-212), and the 5-HT3 receptor antagonist ondansetron. d-Fenfluramine (0.3-3.0 mg/kg) did not reduce 0.9% saline preference; instead, at 0.3 mg/kg there was a significant increase in saline drinking. In contrast, MK-212 (0.3-3.0 mg/kg) abolished the preference for isotonic saline whereas ondansetron (10-100 micrograms/kg) had no effect. d-Fenfluramine and MK-212 reduced hypertonic saline drinking, although at the highest dose for each drug water drinking was also reduced. These data add further to the evidence for an important serotonergic involvement in the control of saline drinking and preference in the rat.