In the seventh year of this project, we continued our focus on developmental aspects of fear in rodent pups. Previously, we studied the role of opiate, benzodiazepine, corticotropin-releasing factor, and serotonin neural systems in the modulation of the rat pup's response to social isolation. In this past year we have focused on the role of excitatory amino acid receptors in regulating a key aspect of the behavioral response to social separation--the ultrasonic isolation call. Compounds which decrease activation of the NMDA coupled cation channel, including functional antagonists at both the NMDA receptor and the strychnine-insensitive glycine receptor, reduce the number of isolation calls in 1 0 day old rat pups. As these pharmacologic effects appear similar to the benzodiazepines in both their efficacy and their specificity, these results -suggest that some of these agents, particularly those that bind to the glycine modulatory site, may provide an entirely new class of anxiolytics for clinical use. In related experiments, we mapped the various subtypes of excitatory amino acid receptors through ontogeny in the rat brain. We also embarked on a comparative approach to the study of separation distress. Species with contrasting styles of affiliation in adulthood were compared for differences in separation responses in development. During a 5 minute isolation test, pups from a monogamous, highly affiliative rodent, the prairie vole, gave more isolation calls and a greater corticosterone response than pups from a less affiliative congener, the montane vole. These results have suggested that separation distress during development may be a reflection of species typical patterns of social bonding and not simply a measure of individual reactivity.
