Mood-stabilizing effects of rapamycin and its analog temsirolimus: relevance to autophagy.

Accumulated data support a relationship between mood disorders and cellular plasticity and resilience, some suggesting relevance to autophagy. Our previous data show that pharmacological enhancement of autophagy results in antidepressant-like effects in mice. The current study was designed to further examine the effects of autophagy enhancement on mood by testing the effects of subchronic treatment with the mammalian target of rapamycin (mTOR) inhibitors and autophagy enhancers rapamycin and temsirolimus in a model for mania and in a model for antidepressant action, respectively. The results show that rapamycin reduced mania-like aggression and reward-seeking behaviors, with no effects on locomotion. Temsirolimus reduced depression-related immobility in the forced-swim test without effects on locomotion in the open field or on anxiety-related measures in the elevated plus maze. Taken together with our previous findings, these data support the notion that enhancing autophagy may have mood-stabilizing effects.