Page - (000173) - in Biomedical Chemistry: Current Trends and Developments

involved in stimulus conditioned responsiveness (Bassareo, 2002) and locomotor activity. The mesocortical pathways of dopaminergic projections arise mainly from the VTA and medial SN, densely innervating the prefrontal, cingulated, suprarhinal and entorhinal cortices, and the dorsal and ventral hippocampus and the visual cortex. Dopamine was described to act in the prefrontal cortex (PFC), by modulating signals received from relevant thalamic afferents (Thierry, 1988). Under stressful situations, dopamine metabolism is increased in the PFC and, therefore, dopamine seems to be also relevant in plastic responses to cope with the stressors (Sullivan, 1998; 2004). Dopamine is also involved in the control of memory-guided behavior in the prefrontal cortex (Goldman-Rakic, 1992) and in cognitive tasks (Weinberger, 1988; Puig, 2014). It is noteworthy that these pathways are under a complex net of direct stimulation and feedback regulation within the dopaminergic system. In the CNS, serotonin (5-hydroxytriptamine, 5-HT) is a key player in mood control. Alterations in 5-HT function have been implicated in several clinical states, including affective disorders, obsessive- compulsive disorders, schizophrenia, anxiety states, phobic disorders, eating disorders, migraine, and sleep disorders (Stockmeier, 2003; Albert, 2014). There is also evidence that 5-HT is involved in learning and memory processes (Meneses, 1999; Faulkner, 2014). The majority of serotonergic neurons are located in the midline raphe nuclei (Tork, 1990). Serotonergic neurons in the raphe nuclei have extensive projections to virtually all areas of the brain and spinal cord (Tork, 1990), but the brain regions usually implicated in cognition and mood receive 5-HT projections mainly from the dorsal raphe nucleus (DRN) and median raphe nucleus (Halliday, 1995). The majority of the ascending 5-HT fibers originate at MRN or DRN, while a caudal cluster gives rise to almost all the descending 5-HT fibers (Steinbusch, 1981; Halliday, 1995). The early development of the 5-HT cell bodies and their extensive net of connections through all the brain, are indicative of the important role that serotonin plays in the development and functioning of the CNS. Diencephalic structures, the basal forebrain, septal regions, hippocampal formation and the cerebellum all receive ascending projections from the DRN and MRN (Halliday, 1995). These projections