Excitatory amino acid-induced drinking in pigeons: Pharmacological and physiological aspects.

Abstract

Intramuscular administration of the excitatory amino acid (EAA) agonists NMDA (N-methyl-D-aspartate) and kainate, but not AMPA ($\alpha$-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid), elicited copious drinking in pigeons. The competitive NMDA antagonist, CGS 19755 (cis-4-phosphonomethyl-2-piperidine carboxylic acid), and the uncompetitive NMDA antagonists, PCP (phencyclidine) and MK-801 (dizocilpine) blocked dipsogenic effects of NMDA but not those of kainate or water deprivation. Centrally administered CGS 19755 blocked dipsogenic actions of NMDA at doses approximately 2000-fold lower than systemic doses. Thus, NMDA-induced drinking appears to be mediated by centrally located NMDA-receptors, whereas kainate-induced drinking does not appear to be mediated by NMDA receptors. Although NMDA caused some water loss, it appears that somatic dehydration was not the major stimulus to drink following NMDA administration. Neither NMDA nor kainate produced increases in plasma osmotic pressure (i.e., cellular dehydration) which could account for the drinking produced by these compounds. Whereas angiotensin II (ANG II) caused large pressor effects, neither NMDA nor kainate did so. The angiotensin converting enzyme inhibitor, captopril did not attenuate drinking produced by NMDA or kainate, whereas captopril blocked drinking induced by the ANG II precursor, ANG I. Therefore, it appears that ANG II does not mediate EAA-induced drinking. The competitive NMDA antagonist CGS 19755 was ineffective in reducing drinking elicited by NaCl, LiCl, extracellular dehydration, or ANG II, suggesting that NMDA receptors were not necessary for the expression of drinking caused by any of these stimuli. Drinking in pigeons is a novel effect of NMDA and kainate which lends itself well to the examination of EAA pharmacology in vivo as a simple behavioral assay which requires no extensive training and is repeatable within subjects. EAA-induced drinking may also provide further information about the neuropharmacological control of water balance.