5-HT2a receptor modulation of cognitive flexibility

The ability to modify the behavioral response due to change of contingencies in the environment is defined as cognitive flexibility and it is a core component of the executive functions, those which relies heavily on the prefrontal cortex. Importantly impairment in cognitive flexibility has been reported in several neurodegenerative and neuropsychiatric disorders, including Alzheimer’s disease and schizophrenia. The serotoninergic system (5-HT) plays a crucial role modulating prefrontal cortical functions. Among the most densely expressed serotonergic receptors is the 5-HT2a receptor (5-HT2aR), which has been implicated in executive functions like goal-directed behaviors , impulse control and behavioral adaptation. Previous pharmacological evidence suggests that the 5-HT2AR contributes to cognitive flexibility. However, the precise contribution of this receptor, particularly the consequences of constitutive loss of 5-HT2AR signaling, remains to be analyzed. The aim of this project is to analyze the role of 5-HT2aR in cognitive flexibility. For this we use a genetically modified mouse model backcrossed into the C57B/6 strain that has knocked out the 5-HT2aR. We first characterized this animal model through a battery of behavioral tests that includes the Open Field Test, the Light/Dark Box Test and the Forced Swim Test. Subsequently, by using the T-Maze for a reversal learning task we assessed and compared the wild type and the knockout animals.