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Some researchers have suggested that dopamine systems in the mesolimbic pathway may contribute to the 'positive symptoms' of schizophrenia, [1] [2] whereas problems concerning dopamine function within the mesocortical pathway may be responsible for the 'negative symptoms', such as avolition and alogia. [3]
The mesolimbic pathway is a collection of dopaminergic (i.e., dopamine-releasing) neurons that project from the ventral tegmental area (VTA) to the ventral striatum, which includes the nucleus accumbens (NAcc) and olfactory tubercle. [9] It is one of the component pathways of the medial forebrain bundle, which is a set of neural pathways that ...
Each pathway is a set of projection neurons, consisting of individual dopaminergic neurons. The four major dopaminergic pathways are the mesolimbic pathway, the mesocortical pathway, the nigrostriatal pathway, and the tuberoinfundibular pathway. The mesolimbic pathway and the mesocortical pathway form the mesocorticolimbic system.
D 2 Receptor: Hyperactive dopaminergic activity on D 2 receptors in the mesolimbic pathway is responsible for the positive symptoms of schizophrenia (hallucinations, delusions, paranoia). After taking an antipsychotic, antagonism of D 2 receptors occurs throughout the entire brain, leading to a number of deleterious side effects from D 2 ...
It is unclear, however, how nicotine interacts with positive symptoms, as it would follow from this theory that nicotine would exacerbate excess dopamine in the mesolimbic pathway and thus positive symptoms as well. One theory argues that the beneficial effects of nicotine on negative symptoms outweigh possible exacerbation of positive symptoms.
[4] [3] [1] [5] Damage to the anterior cingulate cortex and to the striatum, which includes the nucleus accumbens and caudate nucleus and is part of the mesolimbic dopamine reward pathway, have been especially associated with DDM.
There is evidence for increased activity of the mesolimbic pathway, a dopaminergic pathway, in schizophrenia patients. This comes from the discovery of increased L-DOPA decarboxylase levels in the brains of these patients. L-DOPA decarboxylase is an enzyme which converts L-DOPA to dopamine by removing a carboxyl group. [8]
A 5-HT 2C agonist may be expected to reduce positive symptoms of schizophrenia by reducing dopamine release in the mesolimbic dopamine pathway. Vabicaserin (SCA-136) is a 5-HT 2C agonist that has shown promise in preliminary testing for the treatment of schizophrenia. [42]