Serotonin has long been recognized as a neurotransmitter in the mammalian central nervous system, and as such has been implicated in a variety of behavioral functions. While substantial knowledge has accumulated regarding the biochemical processes involved in its synthesis, release and reuptake, its localization in the central nervous system and its binding sites, relatively little is still known about its postsynaptic actions, their pharmacology and their ionic and molecular bases. This application proposes, therefore, to examine the effects of serotonin in two regions of the mammalian brain; the hippocampus and prefrontal cortex. Based upon binding studies it has been proposed that these two areas are particularly enriched in the two best known subtypes of serotonin binding sites and therefore are potentially ideal locations to study serotonergic receptors and their mechanisms of actions. Four issues will be addressed in these areas: 1) the electrophysiological actions of serotonin; 2) the pharmacology of the serotonin receptor involved in these actions; 3) the final effector mechanisms responsible for the observed effects; and 4) the transmembrane signalling mechanism used by these receptors. These studies will be conducted using intracellular recordings in in vitro rat brain slices and will involve the use of current and voltage clamp methods. This study should elucidate some of the mechanisms involved in the actions of serotonin in the central nervous system and therefore should ccontribute significantly to our present understanding of serotonergic functions in the central nervous system as well as its associated pathological states.
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