Naloxone antagonizes the hyperdipsic effect of sulpiride in a salt-preference test in male and female rats.

The consumption of saline and water in a two-bottle test of salt-preference was measured after the administration of sulpiride, a dopamine receptor antagonist and of naloxone, an antagonist at opiate receptors. The two drugs were injected alone, or in combination. Three concentrations of saline (0.125, 0.6 and 1.7% NaCl solutions) were used and the tests were carried out using both male and female, water-deprived rats. When the rats were allowed the choice between a highly-preferred 0.125% NaCl solution and water, sulpiride (30 mg kg-1, i.p.) produced an increase in the intake of the two fluids. When naloxone (1 mg kg-1, s.c.) was given alone, it had no effect in this test of salt preference, but when given in combination, completely eliminated the hyperdipsic effect of sulpiride, providing behavioural evidence of a significant interaction between sulpiride and naloxone. When choices of either 0.6 or 1.7% NaCl solutions and water were given, the baseline levels of the consumption of the fluids were increased. Under these circumstances, sulpiride did not significantly increase the consumption of fluids; instead, naloxone significantly reduced the level of fluid consumption. In a further experiment, apomorphine, at dose levels which stimulate dopamine autoreceptors, had no effect on either fluid intake or saline preference in water-deprived male rats. Biochemical data showing that dopamine inhibits the release of beta-endorphin in the hypothalamus through the dopamine D-2 receptor, suggests a possible mechanism for a blockade of sulpiride-induced hyperdipsia by naloxone.