The effects of an adenosine A(2A) agonist as an adjunctive treatment to alleviate sensorimotor gating deficits in a rodent model of schizophrenia

• Main Author: Rauhuff, Hannah
• Format: Others
• Published: Digital Commons @ East Tennessee State University 2020
• Subjects: Mental Disorders; Pharmaceutics and Drug Design
• Online Access: https://dc.etsu.edu/honors/566; https://dc.etsu.edu/cgi/viewcontent.cgi?article=1679&context=honors

The adenosine system has become a promising target for the treatment of schizophrenia due to its unique relationship with dopamine D2 receptors. Dopamine D2 receptors display heightened sensitivity in schizophrenia, and inhibition of these receptors has been shown to alleviate some of the psychotic symptoms of the disorder. Inhibition of adenosine A(2A) receptors has been shown to decrease dopamine D2 receptor sensitivity, making this receptor a potential target for treatment of the disorder. This effect occurs because adenosine A(2A) receptors form a mutually inhibitory heterodimeric complex with dopamine D2 receptors. The present study looked at the effects of an adenosine agonist on prepulse inhibition (PPI) and cyclic-AMP response binding element protein (CREB) concentrations in the nucleus accumbens (NAc) using a rodent model of schizophrenia (NQ model) that presents with increased D2 receptor sensitivity. Results showed that the A(2A) agonist was effective in improving PPI in NQ-treated animals. The agonist was also effective in reducing increased CREB concentrations in the NAc of NQ-treated animals to control levels. The effectiveness of the agonist suggests that the adenosine system may be a viable target for the treatment of some of the psychotic symptoms associated with schizophrenia.