The dopamine (DA) innervation of the prefrontal cortex (PFC) differs from other mesotelencephalic DA terminal field regions in that it responds in a quantitatively different manner to a number of pharmacological and environmental manipulations. The quantitatively different response characteristics of the PFC DA system and the resultant pattern of changes across the mesotelencephalic DA terminal fields presumably reflect differences in the regulatory features of mesencephalic neurons, which give rise to the DA innervations of different forebrain regions. The regulatory controls involved in the normal impulse-dependent release of DA from the nerve terminal range from intrinsic regulatory features to extrinsic regulatory features. This chapter explores the features of mesoprefrontal cortical DA neurons that render their response characteristics to a number of pharmacological and environmental challenges different from those of other mesotelencephalic DA neurons by using stress-induced alterations in mesotelencephalic DA neurons as a model. It also examines both the similarities and differences between DA neurons projecting to the PFC and those innervating other telencephalic sites.
