What is the Mesolimbic Pathway?
The mesolimbic pathway is a brain circuit that depends on the neurotransmitter dopamine. It enables habit formation by linking certain behaviors to the sensation of pleasure. For this reason, it is also called the brain's reward pathway and is a focus of research on drug addiction. Since dopamine malfunction has been associated with schizophrenia and movement disorders, medication treating these diseases interacts with the mesolimbic pathway in complex ways that sometimes result in psychiatric and physical side effects.
Within the central nervous system, the mesolimbic pathway runs from the ventral tegmental area of the midbrain through the limbic system of the temporal lobe — the hippocampus, amygdala, and nucleus accumbens. The last structure is responsible for the release of dopamine that signals pleasure or reward to many brain regions. Neurotransmitters like GABA and glutamate also moderate the action of the pathway, but its primary functions are affected by neurons that respond to dopamine. In rodents, destruction of the mesolimbic circuit results in loss of addictive cravings, motivation, and increased lethargy.
The reward system of the brain modulates behavior through pleasure, operating in tandem with a similar fear and aversion circuit that provides negative feedback for unpleasant situations. When a pleasurable stimulus is experienced, the mesolimbic pathway is activated, causing the nucleus accumbens to release dopamine. Emotional and learning circuits are activated as well, linking the stimulus to the positive feelings involved. Major drugs and even enjoyable habit-forming activities trigger the increase of mesolimbic activity. Over time the brain becomes desensitized, and greater amounts of the neurotransmitter must be released to provide the same experience of pleasure.
Some scientists argue that schizophrenia derives from a disturbance of the mesocortical and mesolimbic pathway. Called the dopamine hypothesis, this is a controversial debate in psychopharmacology. Proponents point out that many antipsychotic drugs used in psychiatry block the binding of dopamine to its neuronal receptors, and note the schizophrenia-like side effects of drugs used to enhance dopaminergic pathways for the treatment of Parkinson's disease. Critics raise evidence that shows some drugs reduce psychosis without having a clear mechanism, and that the reduction in dopamine levels does not immediately improve symptoms. They also argue that individual brains may be changed by stress or other environmental conditions.
Upregulation or increased sensitivity of the mesolimbic pathway can occur in response to certain psychiatric medications. Some patients experience a relatively rare surge in their psychiatric symptoms, resulting in intensified psychosis. Called tardive dysphrenia, the problem can manifest after patients take certain antipsychotic drugs acting on the mesolimbic pathway, usually by blocking receptors. Since dopamine is also important for the control of the nigrostriatal motor pathway, antipsychotics can affect neuromuscular function by blocking this circuit, causing the spastic involuntary movements characterizing tardive dyskinesia.
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