Chronic Forced and Free Exercise on Cocaine Place Conditioning and Glutamatergic Synaptic Plasticity in the VTA

Exercise may be useful in preventing substance use disorders and addiction. It is well known that chronic exercise, both forced and voluntary, decreases addiction vulnerability in rodent models and likely in humans. However, the mechanism by which chronic exercise accomplishes this has not been fully evaluated. Here, a conditioned place preference (CPP) paradigm was used to measure the learning of cocaine-associated environmental cues in two groups of rats following a period of both forced and free running. It is shown that rats subjected to chronic forced running displayed no significant deviation in learning of contextual cues paired with cocaine through CPP. On the other hand, rats subjected to chronic free running displayed a notable decrease in acquisition of cocaine-CPP. To investigate the mechanism by which chronic exercise affects cocaine-CPP, we will conduct future electrophysiological studies in the ventral tegmental area (VTA), an area that has been widely implicated in the natural reward circuitry of the brain. The VTA and its role in addiction has been studied extensively by the Morikawa Lab, with one previous study finding that repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine-CPP. Essentially, we expect to observe a decrease in long-term potentiation (LTP) of NMDA-mediated glutamatergic synaptic plasticity in the VTA and consequently, a decrease in cocaine-CPP following both chronic forced and free exercise. If observed, our findings will suggest that decreased plasticity of glutamatergic transmission may be responsible for decreased addiction vulnerability through chronic exercise.