| First Author | Santini MA | Year | 2011 |
| Journal | Neuroscience | Volume | 190 |
| Pages | 251-7 | PubMed ID | 21664256 |
| Mgi Jnum | J:175651 | Mgi Id | MGI:5286806 |
| Doi | 10.1016/j.neuroscience.2011.05.048 | Citation | Santini MA, et al. (2011) Novelty-induced activity-regulated cytoskeletal-associated protein (Arc) expression in frontal cortex requires serotonin 2A receptor activation. Neuroscience 190:251-7 |
| abstractText | Many psychiatric disorders are characterized by cognitive and emotional alterations that are related to abnormal function of the frontal cortex (FC). FC is involved in working memory and decision making and is activated following exposure to a novel environment. The serotonin 2A receptor (5-HT(2A)R) is highly expressed in the FC where its activation induces hallucinations, while blockade of 5-HT(2A)Rs contributes to the therapeutic effects of atypical antipsychotic drugs. The purpose of the present study was to investigate the involvement of 5-HT(2A)R in FC activation following exposure to a novel environment. As an output of FC activation we measured expression of activity-regulated cytoskeletal-associated protein (Arc). Novelty-exposure (open-field arena) robustly up-regulated FC Arc mRNA expression ( approximately 160%) in mice compared to home-cage controls. This response was inhibited with the 5-HT(2A)R antagonists ketanserin and MDL100907, but not with the selective 5-HT(2C)R antagonist SB242084. Novelty-exposure also induced Arc mRNA expression in hippocampus ( approximately 150%), but not in cerebellum or brainstem. Pretreatment with 5-HT(2A)R antagonist ketanserin did not repress the Arc induction in hippocampus, indicating that the involvement of 5-HT(2A)R in this response is restricted to the FC. Similarly, the novelty-induced stress as determined by increasing levels of plasma corticosterone, was not influenced by 5-HT(2A)R antagonism suggesting that Arc mRNA and stress are activated via distinct mechanisms. Taken together, our results demonstrate that the induction of Arc in the FC following exposure to a novel environment is dependent on the 5-HT(2A)R, and that the simultaneous release of corticosterone is regulated via another system independent of 5-HT(2A)R activation. |
