persistent increases in 5-HT neurotransmission, via drugs or SERT gene deletion, increase the occurrence of 5-HT2CR mRNA editing events, while at the same time decreasing 5-HT2CR responsiveness [52,87,88]. Interestingly, acute bouts of physical activity (albeit forced) can also increase central 5-HT [89]. It is possible that there is an overlap between some of the underlying mechanisms of therapeutic drugs and exercise, such that persistent changes in 5-HT neurotransmission over extended periods of time, whether due to a regular drug regimen or exercise program, can produce long-term plastic changes in the function of post-synaptic modulators of behavior such as the 5-HT2CR. In addition to changing mRNA levels in discrete brain regions, exercise may also affect 5-HT2CR pre-mRNA editing events, which could contribute to our observed reduction in the expression of anxiety- and depression-like behaviors. 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PLOS ONE | www.plosone.org 9 September 2012 | Volume 7 | Issue 9 | e46118