Timing Critical for Using Exercise as Drug Addiction Intervention

Slides show adult hippocampal neurogenesis in mouse models from (A) four different groups and (B) in runner group. Photo courtesy Martina Mustroph.
Slides show adult hippocampal neurogenesis in mouse models from (A) four different groups and (B) in runner group. Photo courtesy Martina Mustroph.

Could exercise have beneficial effects for treating drug addiction, such as have been shown for disease prevention and improving cognitive health? Research from the laboratory of Justin Rhodes shows the answer is, potentially yes, but that answer is dependent upon when the exercise takes place.

Could exercise have beneficial effects for treating drug addiction, such as have been shown for disease prevention and improving cognitive health? Researchers from the laboratory of Justin Rhodes say the answer is, potentially yes, but that answer is dependent upon when the exercise takes place.

Researchers and therapists are exploring exercise as part of a drug rehabilitation program in part because the natural high produced by the body during exercise is seen as a potential substitute for the high addicts get from a drug like cocaine. Researchers from the Rhodes Lab say those hopes may depend on when exercise takes place relative to drug-taking, based on their findings from a study reported in the European Journal of Neuroscience

The researchers wrote that exercise is a “potential intervention for drug addiction because it promotes brain plasticity and may serve as a substitute reward. However, a danger of incorporating exercise into drug rehabilitation programs is that it may strengthen drug learning.”

To test those questions they conducted three studies using mice given exercise and sedentary treatments along with cocaine, and mice given the same treatments and no cocaine. They wanted to determine whether the timing of exercise – either before or after drug exposure – influences the strength of what is called conditioned place preference, which is the place (in this study either grid or hole-textured chambers) the animals prefer after having been conditioned to associate it with cocaine. Experiments using a running wheel and/or enriched environments to test conditioned place preference (CPP) for cocaine had been done before but not to test for its relation to the timing of drug exposure.

Their studies showed, in a first-ever finding, opposite effects of wheel running on cocaine CPP that depend critically on the timing of exercise relative to drug conditioning. The results, they write, suggested that “voluntary exercise strengthens preference for the cocaine-paired texture if exercise is made available prior to drug conditioning” and that, conversely, “exercise appears to weaken preference for the cocaine-paired texture if exercise is made available after conditioning.”

The researchers found that if the animals exercise before the drug conditioning for cocaine, they were better able to learn the association between place and cocaine than sedentary animals. They wrote that just one “drug conditioning session after exercise is sufficient to negate the beneficial effects of an exercise regimen that was completed before drug conditioning. This has important implications for drug relapse.”

“But then it is almost the opposite effect that we found when we had conditioning where we first taught them about the drug-to-context association, and then we let them exercise,” lead author Martina Mustroph of Rhodes’ laboratory said.  “That actually seemed to accelerate the extinction of the drug-to-context preference.”

So, exercise can serve to aid associations involving drug-taking, but could also help in extinguishing those associations – if the association is followed by exercise and the drug-taking is totally eliminated.

 “Taken together,” the researchers wrote, “the results suggest that exercise could be a useful intervention to facilitate extinction of conditioned drug associations during abstinence. However, the benefit of exercise could be reversed if a relapse episode occurred after running had primed the brain for plasticity.”