The Electrophysiological and Biochemical Pharmacology of the Mesolimbic and Mesocortical Dopamine Neurons

Abstract

Since the early pioneering anatomical studies of Dahlstrom and Fuxe (1964), it has been known that midbrain dopamine (DA)-containing neurons project to and innervate not only the striatum but also various limbic regions. These observations and those of Ungerstedt (1971) led to the functional organization of midbrain DA neurons into the nigrostriatal and mesolimbic DA systems. However, in 1973, Thierry and colleagues presented biochemical evidence for the existence of DA in the cerebral cortex, independent of that normally present within the norepinephrine-containing neurons (Thierry et al, 1973a,b). Other work demonstrated that a DA-sensitive adenylate cyclase was present in the cortex (von Hungen and Roberts, 1973). Subsequent anatomical studies, which employed more sensitive fluorescence histochemical techniques, confirmed the presence of a mesocortical DA system (Berger et al., 1974, 1976; Hokfelt et al, 1974; Lindvall et al, 1977, 1978; Lindvall and Bjorklund, 1978a,b). During the last 10 years, much basic electrophysiological, pharmacological, and biochemical research has been directed toward providing a more detailed understanding of the functioning of these midbrain DA systems. The following review is an overview of those studies. The anatomy of these systems will also be discussed, as will the possible roles these systems play in conditioned and unconditioned behaviors. Although it is not within the scope of this discussion to review the nigrostriatal DA system exhaustively, reference will be made to studies of these neurons in order to assess similarities and differences among the midbrain DA pathways. Biochemical, behavioral, and anatomical aspects of the midbrain DA systems have been the topics of reviews in previous volumes of this Handbook (Sedvall, 1975; Iversen, 1977a; Lindvall and Bjorklund, 1978b).