Mesolimbic ventral tegmental area

In 1954, experiments by Olds and Milner revealed that the brain has specialized centers for reward functions. In these studies electrical stimulation of certain brain sites was found to be highly rewarding in the sense that rats operantly respond for electrical stimulation of these brain sites, often to the exclusion of any other activity. A neurotransmitter system that is particularly sensitive to electrical self-stimulation is the mesolimbic dopamine projection that originates in the ventral tegmental area and projects to structures closely... 

In this regard, considerable evidence shows that PCP increases dopaminergic transmission in the striatum (Johnson 1983) and, more recently, evidence indicates that DA function is increased in the mesolimbic and mesocortical pathways as well. For example, PCP administration has been shown to inhibit the firing of cells found in the ventral tegmental area (Freeman and Bunney 1984) similar to that observed in the substantia nigra (Raja and Guyenet 1980). 

Corrigall, W.A., Coen, K.M., Adamson, K.L. Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area. Brain Res. 653 278, 1994. 

Laviolette, S.R., van der Kooy, D. Blockade of mesolimbic dopamine transmission dramatically increases sensitivity to the rewarding effects of nicotine in the ventral tegmental area. Mol. Psychiatry. 8 50, 2003. 

Overall, p agonists increase transmission in the mesolimbic dopamine system (Devine et al. 1993 Johnson and North 1992). They inhibit GABAergic neurons in the ventral tegmental area, disinhibiting dopamine activity. In contrast, k agonists inhibit dopamine release in the same system. As with other drugs of abuse, an influence on the mesolimbic dopamine is believed to mediate the positive reinforcing effects of opioids. 

Yates SL, Bencherif M, Fluhler EN, LippieUo PM (1995) Up-regulation of nicotinic acetylcholine receptors following chronic exposure of rats to mainstream cigarette smoke or alpha 4 beta 2 receptors to nicotine, Biochem Pharmacol 50 2001-2008 Yeomans J, Baptista M (1997) Both nicotinic and muscarinic receptors in ventral tegmental area contribute to brain-stimulation, Pharmacol Biochem Behav 57 915-921 Yoshida M, Yokoo H, Tanaka T, Mizoguchi K, Emoto H, Ishii H, Tanaka M (1993) Facilitatory modulation of mesolimbic dopamine neuronal-activity by a mu-opioid agonist and nicotine as examined with in-vivo microdialysis. Brain Res 624 277-280... 

Willner (1995) provides evidence from many sources that increases or decreases of dopaminergic activity in the mesolimbic system may underpin the pathophysiology of mania and depression respectively. A key area involved may be the subgenual prefrontal cortex which receives extensive reciprocal dopaminergic projections from the ventral tegmental area and substantia nigra and influences dopamine release in the nucleus accumbens (Drevets et al., 1997 see Chapter 16). 

Figure 8. Top. Miller et al. (1983) showed in rats that the neurons in areas 9 (substantia nigra) and 10 (ventral tegmental area at the origin of the mesolimbic and mesocortical projections) fire similarly during all sleep-waking stages (lower curves).

Beitner-Johnson D., Guitart X., and Nestler E.J. (1992) Neurofilament proteins and the mesolimbic dopamine system common regulation by chronic morphine and chronic cocaine in the rat ventral tegmental area./ Neurosci 12(6) 2165-2176. 

The mesolimbic dopamine pathway projects from dopaminergic cell bodies in the ventral tegmental area of the brainstem to axon terminals in limbic areas of the brain, such as the nucleus accumbens (Fig. 10—8). This pathway is thought to have an important role in emotional behaviors, especially auditory hallucinations but also delusions and thought disorder (Fig. 10—9)-... 

A pathway related to the mesolimbic dopamine pathway is the mesocortical dopamine pathway (Fig. 10—10). Its cell bodies arise in the ventral tegmental area of the brainstem, near the cell bodies for the dopamine neurons of the mesolimbic dopa-... 

The mesolimbic system, where the dopaminergic projections originate in the ventral tegmental area, the A10 region, and then spread to the amygdala, pyriform cortex, lateral septal nuclei and the nucleus accumbens. 

The reinforcing (i.e. dependence-producing) effects of cocaine are thought to result from its ability to inhibit the reuptake of dopamine and thereby to increase dopaminergic activity, particularly in the ventral tegmental area and the nucleus accumbens, so enhancing the activity of the dopaminergic system in the mesolimbic area (the reward area) of the brain. 

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