Dopamine Systems

Dopamine-containing neurons of the ventral mesencephalon have been designated as A8, A9, and A10 cell groups: These neurons can be collectively designated as the mesotelencephalic DA system (Dahlström and Fuxe 1964). Historically, the mesolimbic DA system was defined as originating in the A10 cells of the VTA and projecting to structures closely associated with the limbic system. This system was considered separated from the nigrostriatal DA system, which originates from the more lateral substantia nigra (A9 cell group) (Dahlström and Fuxe 1964; Bannon and Roth 1983; Roth et al. 1987; Kalivas 1993; White 1996).

The mesolimbic and mesocortical DA system appear critically involved in modulation of the functions subserved by cortical and limbic regions such as motivation, emotional control, and cognition (Le Moal and Simon 1991). Substantial evidence indicates that the mesolimbic pathway, particularly the DA cells innervating accum-bal areas, is implicated in the reward value of both natural and drug reinforcers, such as sexual behavior or psychostimulants, respectively (Koob 1992; Di Chiara and Imperato 1988; Salamone et al. 2007). Furthermore, animal studies have shown that lesion of DA terminals in the nucleus accumbens induces hypoexploration, enhanced latency in the initiation of motor responses, disturbances in organizing complex behaviors, and inability to switch from one to another behavioral activity (Le Moal and Simon 1991). Hence the mesolimbic DA system seems important for acquisition and regulation of goal-directed behaviors, established and maintained by natural or drug reinforcers (Le Moal and Simon 1991; Kiyatkin 1995).

The medial prefrontal cortex (mPFC) is generally associated with cognitive functions including working memory, planning and execution of behavior, inhibitory response control and maintenance of focused attention (Le Moal and Simon 1991). In addition, the mesolimbic DA pathway is sensitive to a variety of physical and psychological stressors (Roth and Elsworth 1995). Indeed, recent studies have indicated that stress-induced activation of the mesocortical DA neurons may be obligatory for the behavioral expression of such stimuli (Morrow et al. 1999).

The nigrostriatal DA system, which originates from the substantia nigra (A9 cell group), is one of the best studied because of its involvement in the pathogenesis of Parkinson disease (Grace and Bunney 1985). In mammals, the substantia nigra (SN) is a heterogeneous structure that includes two distinct compartments: the substantia nigra pars compacta (SNc) and the substantia nigra pars reticulata (SNr).

The SNc represents the major source of striatal DA and, as already mentioned, its degeneration causes Parkinson disease. On the other hand, the SNr mainly contains y-aminobutyric acid (GABA)-ergic neurons that constitute one of the major efferences of the basal ganglia (Grace and Bunney 1985).

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