Intracranial self-stimulation can be obtained from the prefrontal cortex of the rat. Various hypotheses have been proposed to explain the basis of this behavior. One possible explanation is that the prefrontal cortex projects to catecholamine-containing brain areas to regulate the reward properties of catecholamine neurons. This study attempted to clarify the anatomical relationship between the prefrontal cortex and brain catecholamine systems by tracing the efferent projections revealed after deposition of [35S]methionine into the medial division of the prefrontal cortex of the rat. The results have generally confirmed earlier reports that the efferent projections of the medial prefrontal cortex reach numerous telencephalic, diencephalic, and brainstem structures. A major feature of the output of the medial prefrontal cortex seen in this study was that numerous projections innervate brain areas where there are catecholamine-containing cell bodies and terminals. We observed that particularly prominent projections reach brain areas which correspond to the A-11 and A-13 catecholamine nuclei and innervate portions of the dorsal periventricular catecholamine system. The results of this study are consistent with the hypotheses that the efferent projections of the medial prefrontal cortex could potentially modulate the function of a large number of brain catecholamine nuclei.
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