Adenosine A2A receptor deletion affects social behaviors and anxiety in mice: Involvement of anterior cingulate cortex and amygdala
Abstract Blockade of adenosine A 2A receptors can potentiate motivation to work for natural reinforcers such as food. Conspecific interaction is a potent natural reinforcer in social animals that can be manifested as preference for social exploration versus other sources of novel stimulation. Deficiencies in this type of motivated behavior (social withdrawal) have been seen in several pathologies such as autism and depression. However, the role of A 2A receptors in motivation for social interaction has not been widely explored. Social interaction paradigms evaluate the natural preference of animals for exploring other conspecifics, and the ability to differentiate between familiar versus novel ones. Anxiety is one of the factors that can induce avoidance of social interaction. In the present study, adenosine A 2A knockout (A 2A KO) and wild-type (WT) mice were assessed for social and anxiety-related behaviors. c-Fos immunoreactivity was evaluated as a measure of neuronal activation in brain areas involved in different aspects of motivation and emotional processes. Although A 2A KO mice showed an anxious profile, they displayed higher levels of sociability and were less sensitive to social novelty. WT mice displayed a typical pattern of social recognition 24h later, but not A 2A KO mice, which explored equally both conspecifics. There were no differences between strains in aggressiveness, perseverance or social odor preferences. c-Fos immunoreactivity in A 2A KO mice was higher in anterior cingulate and amygdala compared to WT mice. Thus, A 2A receptors appear to be potential targets for the improvement of pathologies related to social function. Highlights Blockade of adenosine A 2A receptors can potentiate motivation. A 2A KO mice showed anxiety but are more socially oriented. A 2A KO mice were less sensitive to social novelty. c-Fos in A 2A KO mice was higher in anterior cingulate and amygdala than in WT mice. A 2A receptors could be targets for pathologies such as autism and depression.
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