Mesocorticolimbic dopamine

You have to know that we take out most of the mesocorticolimbic dopamine system with that lesion we are not just taking out the nucleus accumbens dopamine projeetion. I am very eareful to put the region of the nucleus accumbens on my slide. 

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]. 

The acute effects of ethanol and other sedative-hypnotics are mediated by actions at a number of receptor systems. For example, ethanol inhibits several excitatory receptor systems, including N-methyl-D-aspartate (NMDA) receptors, kainate receptors, and Ca channels. In addition, ethanol enhances the action of GABA at GABA receptors and appears to modulate serotonergic neurotransmission. Although a component of ethanol reinforcement is mediated by the activation of mesocorticolimbic dopamine neurons, activation of these neurons may not be necessary for ethanol reinforcement, as ethanol remains reinforcing in the absence of these neurons (Samson and Harris, 1992 Koob, 2000b). 

Fibiger, HansC., and Anthony G. Phillips. 1988. "Mesocorticolimbic Dopamine Systems and Reward." Annals of the New York Academy of Sciences 537 206-15. 

White FJ (1996) Synaptic regulation of mesocorticolimbic dopamine neurons. Annu Rev Neurosci 79 405-436. 

Topiramate is an antiepileptic drug that attenuates the rewarding effect of alcohol associated with abuse by inhibiting mesocorticolimbic dopamine release via facilitation of GABA activity and inhibition of glutamate function. It has been demonstrated to reduce both alcohol consumption and craving. 

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