Page - (000172) - in Biomedical Chemistry: Current Trends and Developments

dopamine and dopamine receptors, during developmental periods is long known to alter the standard embryonic development, disrupting neuronal proliferation, cell migration, neuronal maturation, pruning and proper connectivity. Dopaminergic neurons are concentrated in three major cell groups: the substantia nigra (SN) the ventral tegmental area (VTA), and a cell group of dopamine-containing cells in the caudal extension of the SN (Fallon, 1978; 1985a; Deutch, 1988). The SN and VTA regions are strongly implicated in cognition, affective and behavioral disorders (Roeper, 2013), which is partially explained by a relevant overlap with the brain reward and limbic systems (Koob, 1988; 1992). The main efferent connections from the SN-VTA are well described and can be summarized in three groups: the mesostriatal or nigrostriatal projections, the mesolimbic projections and the mesocortical projections (sometimes referred together as mesocorticolimbic). The mesostriatal pathway originates largely from dopaminergic neurons in the ventral sheet of the SNc projecting into the dorsal striatum (Fallon, 1985b; 1988; Voorn, 1988). In the dorsal striatum, dopaminergic terminals synapse with GABAergic and cholinergic neurons, resulting in either excitatory or inhibitory effects depending on the pattern of dopaminergic receptors displayed at the synapse. Dopamine in the dorsal striatum plays an important role in controlling patterns of motor activity, reward-based learning and sequencing, which constitute a complete motor act and represent a cognitive function (Calabresi, 2007; Leisman, 2014). The striatum receives major glutamatergic inputs from the cortex and can control dopaminergic neurons in the SN-VTA through striatal feedback projections (Voorn, 1988; Robbins, 1992; Calabresi, 2000). The mesolimbic pathway arises predominantly from the dorsal sheet of the SNc, SNl and dorsal VTA (Fallon, 1995). These projections innervate, among other areas, the amygdala, and the nucleus accumbens (Fallon, 1985b; 1988), which plays a major role in the limbic-motor integration (Nicola, 2000), underlying complex adaptive behaviors involved in brain stimulation reward and self-administration of psychoactive drugs (Woodward, 1999; Schramm, 2002). In the nucleus accumbens, DA seems to modulate limbic hippocampal and amygdalar inputs (Mogenson, 1988). Dopamine in this brain region was also shown to be