Mesolimbic pathway

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"Reward center" redirects here. For the reward system which contains this pathway, see Reward system.
The mesolimbic pathway can be seen here as the blue projections from the VTA to the nucleus accumbens.

The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain.[1] The pathway connects the ventral tegmental area, which is located in the midbrain, to the nucleus accumbens. The mesolimbic pathway releases dopamine into the nucleus accumbens, where it affects motivation for rewarding stimuli (i.e., incentive salience), the subjective perception of pleasure, and reward-related motor function learning.[2][3][4] It is the most significant neural pathway in the brain in which changes occur in all known forms of addiction.[1][5][6][7]

Anatomy[edit]

The following structures are considered to be a part of the mesolimbic pathway:

Ventral tegmental area
The ventral tegmental area (VTA) is a part of the midbrain. It consists of dopaminergic, GABAergic, and glutamatergic neurons.[8] The VTA communicates with the nucleus accumbens via the medial forebrain bundle.
Nucleus accumbens
The nucleus accumbens is found in the ventral striatum and is composed of medium spiny neurons.[9][10] It is subdivided into limbic and motor subregions known as the shell and core.[8] The medium spiny neurons receive input from both the dopaminergic neurons of the VTA and the glutamatergic neurons of the hippocampus, amygdala, and medial prefrontal cortex. When they are activated by these inputs, the medium spiny neurons' projections release GABA onto the ventral pallidum.[8] The release of dopamine in this structure drives the mesolimbic system.

Clinical significance[edit]

This pathway plays a central role in the neurobiology of addiction;[5][6][7] in particular, a drug addiction is defined as the compulsive use of a drug that is rewarding (i.e., activate this pathway), despite adverse consequences.[8][11] It is also implicated in schizophrenia and depression.[12][13][14] Addiction, schizophrenia, and depression all involve distinct structural changes within this pathway.[12]

Other dopamine pathways[edit]

The other dopamine pathways are:

See also[edit]

References[edit]

  1. ^ a b Dreyer JL (2010). "New insights into the roles of microRNAs in drug addiction and neuroplasticity". Genome Med. 2 (12): 92. doi:10.1186/gm213. PMC 3025434Freely accessible. PMID 21205279. 
  2. ^ Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY, eds. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 147–148, 367, 376. ISBN 978-0-07-148127-4. VTA DA neurons play a critical role in motivation, reward-related behavior (Chapter 15), attention, and multiple forms of memory. This organization of the DA system, wide projection from a limited number of cell bodies, permits coordinated responses to potent new rewards. Thus, acting in diverse terminal fields, dopamine confers motivational salience (“wanting”) on the reward itself or associated cues (nucleus accumbens shell region), updates the value placed on different goals in light of this new experience (orbital prefrontal cortex), helps consolidate multiple forms of memory (amygdala and hippocampus), and encodes new motor programs that will facilitate obtaining this reward in the future (nucleus accumbens core region and dorsal striatum). In this example, dopamine modulates the processing of sensorimotor information in diverse neural circuits to maximize the ability of the organism to obtain future rewards. ...
    The brain reward circuitry that is targeted by addictive drugs normally mediates the pleasure and strengthening of behaviors associated with natural reinforcers, such as food, water, and sexual contact. Dopamine neurons in the VTA are activated by food and water, and dopamine release in the NAc is stimulated by the presence of natural reinforcers, such as food, water, or a sexual partner. ...
    The NAc and VTA are central components of the circuitry underlying reward and memory of reward. As previously mentioned, the activity of dopaminergic neurons in the VTA appears to be linked to reward prediction. The NAc is involved in learning associated with reinforcement and the modulation of motoric responses to stimuli that satisfy internal homeostatic needs. The shell of the NAc appears to be particularly important to initial drug actions within reward circuitry; addictive drugs appear to have a greater effect on dopamine release in the shell than in the core of the NAc.
     
  3. ^ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 10: Neural and Neuroendocrine Control of the Internal Milieu". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 266. ISBN 978-0-07-148127-4. Dopamine acts in the nucleus accumbens to attach motivational significance to stimuli associated with reward. 
  4. ^ Berridge KC, Kringelbach ML (May 2015). "Pleasure systems in the brain". Neuron. 86 (3): 646–664. doi:10.1016/j.neuron.2015.02.018. PMC 4425246Freely accessible. PMID 25950633. 
  5. ^ a b Robison AJ, Nestler EJ (November 2011). "Transcriptional and epigenetic mechanisms of addiction". Nat. Rev. Neurosci. 12 (11): 623–637. doi:10.1038/nrn3111. PMC 3272277Freely accessible. PMID 21989194. ΔFosB has been linked directly to several addiction-related behaviors ... Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states. 
  6. ^ a b Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, Giordano J, Oscar-Berman M, Gold M (2012). "Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms". J. Psychoactive Drugs. 44 (1): 38–55. doi:10.1080/02791072.2012.662112. PMC 4040958Freely accessible. PMID 22641964. It has been found that deltaFosB gene in the NAc is critical for reinforcing effects of sexual reward. Pitchers and colleagues (2010) reported that sexual experience was shown to cause DeltaFosB accumulation in several limbic brain regions including the NAc, medial pre-frontal cortex, VTA, caudate, and putamen, but not the medial preoptic nucleus. Next, the induction of c-Fos, a downstream (repressed) target of DeltaFosB, was measured in sexually experienced and naive animals. The number of mating-induced c-Fos-IR cells was significantly decreased in sexually experienced animals compared to sexually naive controls. Finally, DeltaFosB levels and its activity in the NAc were manipulated using viral-mediated gene transfer to study its potential role in mediating sexual experience and experience-induced facilitation of sexual performance. Animals with DeltaFosB overexpression displayed enhanced facilitation of sexual performance with sexual experience relative to controls. In contrast, the expression of DeltaJunD, a dominant-negative binding partner of DeltaFosB, attenuated sexual experience-induced facilitation of sexual performance, and stunted long-term maintenance of facilitation compared to DeltaFosB overexpressing group. Together, these findings support a critical role for DeltaFosB expression in the NAc in the reinforcing effects of sexual behavior and sexual experience-induced facilitation of sexual performance. ... both drug addiction and sexual addiction represent pathological forms of neuroplasticity along with the emergence of aberrant behaviors involving a cascade of neurochemical changes mainly in the brain's rewarding circuitry. 
  7. ^ a b Olsen CM (December 2011). "Natural rewards, neuroplasticity, and non-drug addictions". Neuropharmacology. 61 (7): 1109–22. doi:10.1016/j.neuropharm.2011.03.010. PMC 3139704Freely accessible. PMID 21459101. 
  8. ^ a b c d Pierce RC, Kumaresan V (2006). "The mesolimbic dopamine system: The final common pathway for the reinforcing effect of drugs of abuse?". Neuroscience and Biobehavioral Reviews. 30: 215–38. doi:10.1016/j.neubiorev.2005.04.016. 
  9. ^ Zhang TA, Maldve RE, Morrisett RA (2006). "Coincident signaling in mesolimbic structures underlying alcohol reinforcement". Biochemical Pharmacology. 72: 919–27. doi:10.1016/j.bcp.2006.04.022. 
  10. ^ Purves D et al. 2008. Neuroscience. Sinauer 4ed. 754-56
  11. ^ Janhunen S, Ahtee L (2007). "Differential nicotinic regulation of the nigrostriatal and mesolimbic dopaminergic pathways: Implications for drug development". Neuroscience and Biobehavioral Reviews. 31: 287–314. doi:10.1016/j.neubiorev.2006.09.008. 
  12. ^ a b Van , den Heuval DMA, Pasterkamp RJ (2008). "Getting connected in the dopamine system". Progress in Neurobiology. 85: 75–93. doi:10.1016/j.pneurobio.2008.01.003. 
  13. ^ Laviolette SR (2007). "Dopamine modulation of emotional processing in cortical and subcortical neural circuits: evidence for a final common pathway in schizophrenia?". Schizoprenia Bulletin. 33: 971–981. doi:10.1093/schbul/sbm048. 
  14. ^ Diaz J. 1996. How Drugs Influence Behavior: A Neurobehavorial Approach. Prentice Hall

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