The Society for Neuroscience spotlights the dissertation research of graduate, Kenny Thiel
Press release from the Society for Neuroscience spotlights the dissertation research of Behavioral Neuroscience graduate student, Kenny Thiel
Recent work from our laboratory reveals that environmentally enriched housing conditions introduced during cocaine abstinence reduces the degree to which drug-associated cues elicit motivation for cocaine. Our findings suggest that environmental enrichment may provide a useful behavioral-based intervention strategy to blunt cue-induced craving, which may in turn help prevent relapse.
A particularly troubling characteristic of drug addiction is relapse, which can occur even after long periods of abstinence. A major contributing factor to relapse is drug craving, which can be triggered by cues (e.g., a crack pipe) that become strongly associated with drug use. Interestingly, over weeks of abstinence, cue-elicited drug craving has actually been shown to intensify over time, making it increasingly difficult to abstain from drug use. These findings underlie the importance of examining treatment strategies that reduce the impact of drug-related cues. Previous animal models of addiction have examined environmental enrichment housing as a preventative strategy against drug use. These studies have shown that enrichment blunts the development of a drug habit relative to standard housing conditions. Our research extends these findings by examining enrichment as an intervention against an already established cocaine habit. To this end, we have found that enrichment introduced during a period of forced abstinence in rats blunts subsequent cocaine-seeking behavior, suggesting a reduction in cue-elicited motivation for cocaine. Our initial findings have been accepted for publication in the International Journal of Neuropsychopharmacology, and our findings on the time course and changes in the stress hormone, corticosterone, were presented in June at the meeting of the College on Drug Dependence.
Environmental enrichment in our animal model refers to housing conditions in which rats live in spacious cages with ample access to other rats, plastic toys, and running wheels. This is in contrast to our standard single-housing condition in which rats live alone without access to social stimulation or physical exercise. We trained single-housed rats to press a lever to receive cocaine infusions (i.e., self-administration) that were delivered with presentation of light and tone cues (i.e., cocaine-paired cues). Following establishment of cocaine self-administration, rats underwent a period of forced abstinence during which they were divided into groups that either continued to live in single-housing conditions or were placed into enriched environments. After either 1 or 21 days of these abstinence conditions, rats were placed back into their cocaine self-administration environment and were tested for cue-elicited cocaine-seeking behavior, which is defined as lever presses that result in presentation of the cocaine-paired cues, but not cocaine. This measure reflects cue-elicited motivation for the drug.
We found that cocaine-seeking behavior increased after 21 days of abstinence relative to 1 day of abstinence, but that environmental enrichment reduced this behavior regardless of abstinence length. Circulating levels of the stress hormone, corticosterone, were highest in the single-housed rats that underwent 1 day of abstinence, suggesting that beneficial enrichment effects may involve lowering stress associated with acute cocaine withdrawal. Currently, we are conducting additional studies to examine differences in neural activation of brain regions typically involved in craving in order to further elucidate the mechanisms that underlie enrichment effects during short- and longer-term abstinence. Drug addiction continues to take a tremendous health and economic toll on society. Drug treatment strategies have fallen short in their effectiveness in preventing relapse to cocaine use, and new strategies are urgently needed. Our findings suggest that novel behavioral-based treatment strategies may be useful. Providing an individual with an array of social and recreational activities may aid in reducing both physical withdrawal symptoms and emotional dysphoria, and may also have lasting protective effects against relapse.