Considerable evidence indicates that the median raphe nucleus (MR), located in the paramedian tegmentum of the midbrain, plays an important role in the control of behavior. This nucleus is one of the major sources of forebrain serotonin, but contains many nonserotonergic cells as well. Lesions of the MR in rats result in dramatic disturbances in locomotor activity, learning and ingestive behavior, many of which appear unrelated to serotonin depletion. Recently, it has been found that injections of the GABA agonist muscimol into the MR of behaving rats leads to hyperactivity and a large increase in food intake. The experiments proposed here are designed to investigate the functional role of GABA and several other neurotransmitters, including endogenous opiates, within the MR. The effects of acute intra-MR drug injections will be examined on a number of behaviors including locomotor activity, feeding, drinking, and gnawing and the possibility of serotonergic mediation of these effects will be examined. The effects of intra-MR injections of the metabolism of serotonin, dopamine and GABA will be investigated biochemically. Experiments will be conducted aimed at identifying the output pathways from the MR involved in the production of behavioral effects following muscimol injections. Anatomical studies will attempt to identify the projection targets of non-serotonergic MR cells, and the origin of GABAergic and other chemically defined projections to the MR. Serotonin has been implicated in a number of psychiatric and neurologic disorders and degenerative changes have been observed in the MR of patients with Alzheimer's disease. The current studies may thus provide information useful in understanding the nature of the functional disturbances in these disorders.
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