Mesocortical tract

Mesocortical tract

The mesocortical tract shares (with the mesolimbic tract) it's source nuclei in the ventral tegmentum and these project to the neocortex. In this graphic, the lack of dopamine (1) causes a lack of stimulation of the D2 receptors causing the symptoms of social withdrawal and a poor concentration. Note that 5-HT2A receptors are present in the mesocortical system (2). If there is a relative overabundance of serotonin, then less DA is released into the synapse. That is why many newer 'atypical' antipsychotics are not just dopamine-antagonists but also 5HT2a-antagonists.

Such drugs disinhibit presynaptic 5HT2-receptors on mesocortical and nigrostriatal dopaminergic neurons. This enhances the dopaminergic activity in these systems, partly counteracting the suppressive effects of dopamine antagonism. Functionally, 5HT2a-antagonism reduces the extrapyramidal side effects of antipsychotic drugs, and the cognitive and social 'negative symptoms' of schizophrenia.Note that the addition of antipsychotic drugs (3) can block DA activity at the receptor, thereby worsening symptoms of social withdrawal and poor concentration.


The negative symptoms of schizophrenia include symptoms such as anhedonia, bizarre behavior, and delusions. 


By using an antipsychotic to block post-synaptic D2 receptors, negative symptoms are reduced. 


5-HT2A receptor antagonism leads to a minimization of negative symptoms.