Prefrontal Serotonergic Denervation Induces Increase in the Density of 5-HT2A Receptors in Adult Rat Prefrontal Cortex

The 5-HTergic system and particularly 5-HT2A receptors have been involved in prefrontal cognitive functions, but the underlying mechanisms by which the serotonin (5-HT) system modulates these processes are still unclear. In this work, the effects of prefrontal 5-HTergic denervation on the density and expression levels of 5-HT2A receptors were evaluated by immunohistochemical and molecular biology studies in the prefrontal cortex (PFC). The [3H]-Ketanserin binding study revealed an increase in the Bmax, along with no change in the binding affinity (KD) for 5-HT2A receptors. The increase in PFC of 5-HT2A receptor density in response to denervation was accompanied by increase in 5-HT2A receptor mRNA and protein levels. This increase in the number of 5-HT2A receptors may be interpreted as an adaptive plastic change, i.e., hypersensitivity; resulting from the selective pharmacological lesion of the raphe-proceeding 5-HTergic fibers to the PFC. Based on previous evidence, this could be strongly related to the abnormal expression of short-term memory.