Impact of the immunosuppressant rapamycin on amygdala activity and behavior

Abstract

The amygdala, a group of nuclei in the medial temporal lobe, plays an important role in the processing of immune derived signals and the generation of sickness behavior. Here we investigated whether and to what extent treatment with the immunosuppressive drug rapamycin affects amygdala neuronal activity and amygdala-dependent behavior. Rapamycin inhibits the serine/threonine protein kinase mTOR (mammalian target of rapamycin) in T and B lymphocytes and thereby hinders the transition of these cells from G1 to S phase. Our experiments revealed that intraperitoneal administration of rapamycin (3 mg/kg) to adult rats led with a latency of about 90 min to a significant increase in amygdaloid neuronal activity measured by intracerebral electroencephalography as well as to an increase in anxiety-related behavior in the elevated plus maze test. The mechanisms underlying these neuronal and behavioral changes are currently under investigation. Given the pivotal role of the amygdala in mood regulation, associative learning, and modulation of cognitive functions, our findings raise the question whether immunosuppressive therapy may increase the risk for the development of neuropsychiatric diseases.