Glutamatergic neurons of rat medial prefrontal cortex innervating the ventral tegmental area are positive for serotonin 5-HT1A receptor protein

The present study was designed to investigate whether serotonin 5-HT1A receptor protein (5-HT1A receptor-immunoreactivity), is present on cortical pyramidal neurons of the rat medial prefrontal cortex (MPC) innervating the ventral tegmental area (VTA). Recent data stress the role of serotonin 5-HT1A receptors in the pathology of schizophrenia, and in the mechanism of action of novel antipsychotic drugs. It was found that approximately 52% of cells in layers II/III of the MPC whose axons initial segments were immunoreactive for serotonin 5HT1A receptor were also labeled with Fluoro-Gold (FG), a retrograde tracer injected into the VTA, indicating that certain portion of neurons forming glutamatergic innervations of the VTA may be controlled by serotonin 5-HT1A receptors. In deep cortical layers (V/VI) retrogradely labeled neurons never colocalized with serotonin 5-HT1A receptor-mmunoreactivity. These anatomical data indicate that serotonin 5-HT1A receptors might potentially control the excitability and propagation of information transmitted by the pyramidal cells to the VTA. Moreover, our results indicate that the drugs operating via serotonin 5-HT1A receptors in the MPC, might control from this level the release of glutamate in the VTA and restore function of glutamate neurotransmission, whose dysfunction is observed for example in schizophrenia.