N-methyl-D-aspartate glutamate receptor blockade inhibits the sensitization of sodium appetite independent of alterations in salt palatability

Abstract

The intraperitoneal injection (ip) of N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine, MK-801, blocks sodium appetite sensitization in rats. Therefore, NMDA receptors seem important for ingestive behavioral adaptations to episodic or chronic periods of dehydration and salt depletion. Orofacial somatic motor responses to intraoral infusion of salt, in a salt taste reactivity test, can be an index of salt palatability. The objective of the present study was to investigate whether ip injection of MK-801 (0.15 mg/kg) alters orofacial responses to intraoral salt (0.3 M NaCl). In Experiment 1, tests were performed 24 h after subcutaneous injection of the natriuretic/diuretic furosemide and removal of ambient sodium. MK-801 inhibited salt intake by 60% average but did not alter salt palatability, compared with vehicle. In Experiment 2, MK-801 was paired with episodes of rapid-onset (1-h latency) sodium appetite, that is, in response to a combination of furosemide with low-dose captopril, or Furo/Cap. A pairing of MK-801, or its vehicle, with Furo/Cap was performed every other three days, three times. In a post-pairing trial, conducted 3 days after the last pairing, MK-801 history did not alter salt palatability in response to Furo/Cap, although it blocked, as expected, salt intake sensitization. In Experiment 3, MK-801 inhibited food intake in animals deprived of food for 24 h, and the respective meal-associated water intake by 60% average. The results suggest that the inhibitory effect of MK-801 on salt intake sensitization is not dependent on increased salt aversion, but they cannot rule out the participation of a general behavioral inhibition on such an effect.