Toluene-Induced Behavioral Sensitization is Attenuated by Voluntary Physical Exercise and Social Interaction

Toluene-based inhalants found in some common products, such as paint thinner or glues, may be used to induce intoxication. Though addiction may be one of its most detrimental consequences, treatment options are insufficient or limited. Environmental enrichment (EE) refers to housing conditions that enhance sensory, cognitive, and motor stimulation. This paradigm induces beneficial effects in a variety of animal models of brain disorders, and also in animal models of drug addiction. Previous studies have shown that toluene induces behavioral sensitization and that EE treatment can reduce this response. Since EE comprises a variety of elements, the aim of the present study was to group mice into five different types of EE-shaping housing conditions (4 weeks) and to identify which of them are key elements in attenuating toluene-induced behavioral sensitization. The experimental groups were: Standard housing with conspecifics; EE with conspecifics; Toys stimulation with conspecifics; Exercise wheels with conspecifics; and Wheel and toy isolated. Mice in Standard housing and previously exposed to toluene exhibited high locomotor activity, suggesting behavioral sensitization. When animals were exposed to toluene and then housed in EE with conspecifics or Exercise wheels with conspecifics conditions an attenuation of behavioral sensitization was observed ( p < 0.001; 100% and 75% effectiveness, respectively). Toy with conspecifics housing also reduced behavioral sensitization, but in a less proportion than the two previous mentioned treatments ( p < 0.002; 33.5% effectiveness). Mice in the Wheel and toy isolated housing did not show significant changes in the assessed behavior ( p = 0.061; 12.4% effectiveness). We suggest that exercise and social interaction are the key enriched main elements to attenuate toluene-induced behavioral sensitization. Our results advise preclinical strategies for inhalant abuse interventions based on social interactions and physical exercise. Also, they provide guidelines to develop experimental models with diverse environments and groups that lead us to understand the complexity of environmental enrichment.