Environmental enrichment reduces behavioural sensitization in mice previously exposed to toluene: The role of D1 receptors.

Abstract It has been reported that environmental stimuli can positively influence addictive responses and the pharmacological effects of drugs of abuse. In this work, we evaluated the ability of environmental enrichment (EE) to attenuate addictive behaviours in mice after repeated exposure to toluene. We also analysed the role of D1 receptors (D1R) in animals chronically exposed to toluene and in those housed under EE. Mice (Swiss Webster) were exposed to toluene (0, 2000 or 4000 ppm, 30 min a day), and addictive responses were examined in the behavioural sensitization model. The induction of sensitization was evaluated over 4 weeks, and its expression was assessed in animals repeatedly exposed to toluene (0 or 4000 ppm, 30 min a day/4 weeks) and then housed under EE conditions during 4 more weeks. D1R levels were measured under these two experimental conditions in the prefrontal cortex, nucleus accumbens, hippocampus and caudate. The results showed that D1R levels decreased during toluene-induced behavioural sensitization. An increase in D1R levels was found in animals housed in EE conditions, in addition to the attenuated expression of behavioural sensitization. These results indicate that environmental stimulation attenuates addictive behaviour induced by toluene and that dynamic changes in D1R are linked in this response.