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Mesolimbic pathway

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File:Dopamineseratonin.png
Mesolimbic dopaminergic and serotonergic pathways.

The mesolimbic pathway is one of the dopaminergic pathways in the brain. The pathway begins in the ventral tegmental area of the midbrain and connects to the limbic system via the nucleus accumbens, the amygdala, and the hippocampus as well as to the medial prefrontal cortex. It is shown to be involved in modulating behavioral responses to stimuli that activate feelings of reward (motivation) and reinforcement through the neurotransmitter dopamine.[1]

Contents

[edit] Anatomy

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 consist of dopamine, GABA, and glutamate neurons.[2]
  • Nucleus Accumbens
The nucleus accumbens is found in the ventral striatum and is composed of medium spiny neurons.[3][4] It is subdivided into limbic and motor subregions known as the shell and core.[2] 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 the these inputs, the medium spiny neurons' projections release GABA onto the ventral pallidum.[2] The release of dopamine in this structure drives the mesolimbic system.
  • Amygdala
The amygdala is a large nuclear mass in the temporal lobes anterior to the hippocampus. It has been associated with the assignment of emotions, especially fear and anxiety.
  • Hippocampus
The hippocampus is located in the medial portion of the temporal lobes. It is known for its association with memory.

[edit] Controversy of Mesolimbic Dopamine Function

There is controversy about dopamine’s role in the reward system. Three hypotheses—hedonia, learning, and incentive salience—have been proposed as explanations for dopamine’s function in the reward system.[5] The hedonia hypothesis suggest that dopamine in the nucleus accumbens is a 'pleasure neurotransmitter'. Historically, in the late 1970s, it was found that drugs of abuse, worked with dopamine particularly in the nucleus accumbens to cause the "high" or euphoric state. However, not all rewards or pleasurable things cause the reward system to be activated which suggests that the mesolimbic system may not just being a system that works merely off things you like (hedonia).[6] Learning on the other hand deals with predictions of future rewards and associative learning. Studies have shown that rats that have a destroyed ventral tegmental area and nucleus accumbens do not lose their learning abilities but rather lack the motivation to work hard for a reward.[5] Incentive salience (wanting) stands out as a possible role of dopamine because it looks at dopamine as being released when there is stimuli worth working hard for, thus making an individual harder to get it. In self-administration studies, animals have been trained to give an operant response (lever press, nose poke, wheel turn, etc.) in order to obtain either a drug or mate. It has been shown that the animals will continue to do the task until the reward is received or fatigue sets in.[2][6]

[edit] Clinical significance

Since the mesolimbic pathway is shown to be associated with feelings of reward and desire, this pathway is heavily implicated in neurobiological theories of addiction, schizophrenia, and depression.[7][8][9] Drug addiction, the loss of control over drug use or the compulsive seeking and taking of drugs despite adverse consequences, with the five major classes of abused drugs (psychostimulants,opiates,ethanol,cannabinoids, and nicotine) are due to increased dopamine transmission in the limbic system-each by different mechanisms.[2][10] Like drug addiction, schizophrenia and depression have similar structural changes with dopamine transmission.[7]

[edit] Other dopamine pathways

The other dopamine pathways are:

[edit] References

  1. ↑ Tisch S, Silberstein P, Limousin-Dowsey P, Jahanshahi M. 2004. The basal ganglia: anatomy, physiology, and pharmacology. Psychiatric clinincs of North America 27:757+
  2. ↑ 2.0 2.1 2.2 2.3 2.4 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
  3. ↑ Zhang TA, Maldve RE, Morrisett RA. 2006. Coincident signaling in mesolimbic structures underlying alcohol reinforcement. Biochemical Pharmacology 72:919-27
  4. ↑ Purves D et al. 2008. Neuroscience. Sinauer 4ed. 754-56
  5. ↑ 5.0 5.1 Berridge KC. 2007. The debate over dopamine's role in reward: the case for incentive salience. Psychopharmacology 191:391-431
  6. ↑ 6.0 6.1 Neill D. Emory University. Personal Interview. 14 Oct. 2008
  7. ↑ 7.0 7.1 Van den Heuval DMA, Pasterkamp RJ. 2008. Getting connected in the dopamine system. Progress in Neurobiology 85:75-93
  8. ↑ 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
  9. ↑ Diaz J. 1996. How Drugs Influence Behavior: A Neurobehavorial Approach. Prentice Hall
  10. ↑ 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

[edit] See also

[edit] External links


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Neurotransmitter systems
Acetylcholine Basal optic nucleus of Meynert - Hippocampus
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Mesocortical pathway - Mesolimbic pathway

Pars compacta -> Nigrostriatal pathway -> Striatum

Tuberoinfundibular pathway

Locus ceruleus
Raphe nuclei

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Aspartate

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GABA

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Glycine

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Glutamate

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