Effects of environmental enrichment on cocaine addiction-related behaviors in rodents: A systematic review and meta-analysis.

OBJECTIVE

To employ systematic review and meta-analysis methodologies to comprehensively evaluate the integrated effects of Environmental Enrichment (EE) on cocaine addiction-related behaviors in rodents-specifically Conditioned Place Preference (CPP), Self-Administration (SA), and Locomotor Activity (LMA)-thereby providing evidence-based references for elucidating the protective mechanisms of EE and optimizing intervention protocols.

METHODS

Following the PRISMA guidelines, a systematic search was conducted across databases including PubMed, Web of Science, and the Cochrane Library. Two researchers independently performed literature screening, data extraction, and risk of bias assessment. Data were analyzed using a random-effects model with Stata 17.0 software.

RESULTS

A total of 22 independent literature sources (comprising 48 independent animal experimental studies) were included. (1) EE significantly reduced cocaine-induced Conditioned Place Preference (SMD = -0.84, 95% CI: -1.07, -0.61, P < 0.001), showing high consistency among studies (I2 = 0.0%); (2) EE significantly attenuated cocaine Self-Administration behavior (SMD = -0.71, 95% CI: -0.95, -0.47, P < 0.001); (3) EE significantly inhibited cocaine-induced Locomotor Activity (SMD = -1.23, 95% CI: -1.81, -0.65, P < 0.001); (4) Significant heterogeneity was observed in the meta-analyses of Self-Administration (I2 = 60.0%) and Locomotor Activity (I2 = 69.9%). Subgroup analyses revealed that high-frequency toy replacement (frequency > once/week) reduced heterogeneity in the Self-Administration group while maintaining a significant intervention effect; regarding Locomotor Activity, the inhibitory effect of EE was more pronounced with lower heterogeneity in animals that had undergone sensitization induction.

CONCLUSION

Environmental Enrichment effectively attenuates reward memory, cocaine taking and seeking behaviors, and psychomotor sensitization associated with cocaine addiction in rodents. These effects are robust across different developmental stages and intervention timings. The specific implementation details of the intervention protocol, particularly high-frequency toy replacement, are critical moderating factors in reducing heterogeneity and achieving stable, consistent protective efficacy.