Mesocorticolimbic dopamine pathway

Triple reuptake inhibitors (TRIs), which inhibit reuptake at all three transporters, have attracted considerable interest in recent years [77]. The involvement of dopamine reuptake in the etiology of depression and other CNS disorders has been recognized [29,30]. As a result, TRIs have been proposed to offer a faster onset of action and improved efficacy for depression over currently prescribed single or dual action monoamine reuptake inhibitors. Historically, the mesocorticolimbic dopamine pathway is thought to mediate the anhedonia and lack of motivation observed in depressed patients [78,79]. In addition, methylphenidate, both immediate release and extended release formula, has been found to be effective as an augmenting agent in treatment-resistant depression [4]. Furthermore, clinical studies using the combination of bupropion and an SSRI or SNRI have showed improved efficacy for the treatment of MDD in patients refractory to the treatment with SSRIs, SNRIs, or bupropion alone [5,80,81]. 

O Virtually all abused substances appear to activate the same brain reward pathway. Key components of the reward pathway are the dopamine (DA) mesocorticolimbic system that projects from the ventral tegmental area (VTA) and the nucleus accumbens (NA) to the prefrontal cortex, the amygdala, and the olfactory tubercle (Figs. 33-3 and 33-4).5 Animal studies... 

Fig. 2. A. Forebrain dopamine projection system in rodents and primates. The nigrostriatal pathway projects from the A8 and A9 groups of the substantia nigra (SN) via the medial forebrain bundle (mfb) to the neostriatum (NS). The mesocorticolimbic pathway projects from the more medially located A10 cell group of the ventral tegmental area (VTA) to the nucleus accumbens (NAcc) and olfactory tubercle (OT) of the ventral striatum (VS) and limbic forebrain areas including prefrontal cortex (Ctx), septum (Se) and amygdala (A). B. Striatal projection areas in the rodent brain are divided into the more dorsal neostriatum, and ventral striatum. C. In the primate brain, including human and illustrated for the marmoset, the neostriatum is divided by the fibers of the internal capsule into caudate nucleus (CN) and putamen (Pu). Correspondingly, the neostriatum of rats is sometimes designated the caudate-putamen (CPu) complex.

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