There has been an explosive growth in information about glutamate-related excitatory amino acids and their antagonists in the last decade, and it would appear that the interest in these compounds will continue. They are fascinating at a basic science level (e.g., how do they function as neurotransmitters; are they functionally related to each other?) and at an applied level (might they be useful in treating stroke; are they involved in degenerative mental diseases; do they have specific effects on learning and memory; what is the mechanism by which they serve as reinforcers?). Despite the interest in function, the vast majority of studies of these drugs have involved electrophysiological, neuroanatomical, or neuropharmacological procedures. There are a very limited number of selective agonists or competitive antagonists available, and those that do exist often have limited access to the brain. Thus, little is known about their behavioral effects or their function in integrated systems. Although there are difficulties involved in studying many of these drugs at a behavioral level, we propose to continue our efforts in this direction. We will continue to evaluate the noncompetitive NMDA antagonists that act on the PCP receptor site and attempt to understand why some of these drugs, all of which should and most of which do have nearly identical effects, are slightly or markedly different in their behavioral profile. We will attempt to determine whether parenterally administered NMDA acts through central mechanisms or, as some of our data suggest, through peripheral mechanisms to affect behavior. We will evaluate the direct effects of glutamate agonists, given parenterally or centrally, on behavior in the pigeon to characterize these effects and the ability of selective antagonists to block these effects. We will continue to attempt to train NMDA and competitive NMDA antagonists as discriminative stimuli in pigeons and add experiments that attempt to train AMPA and kainate as discriminative stimuli as well. We will continue with efforts to understand the mechanism by which kainate and NMDA increase water intake in pigeons, We will continue to compare competitive NMDA antagonists and noncompetitive NMDA antagonists for their ability to produce anesthesia, act as reinforcers, and produce tolerance and cross-tolerance. Finally, we would like to begin studies that evaluate the effects of these agents on specific attributes of learning and recall in pigeons.
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