Effect of environmental enrichment components on addictive-like behaviour induced by inhalants

Inhalants are volatile substances used for recreational purposes by many populations around the world and are available in common industrial products such, as, solvents, gasoline, varnishes; paint thinner, adhesives and inks. Toluene is the main chemical constituent of these substances used to induce psychoactive effects and its repeated consumption may lead to addiction, particularly in young people. Preclinical studies in animal models have revealed that housing in an environmental enrichment (EE), consisting of physical exercise, cognitive stimulation and social interaction, may reverse some behavioral effects produced by toluene, including its addictive-like responses. However, it is unclear which of the components included in the complex enrichment are responsible for reverse those addictive behaviors. Thus, the objective of this study was to evaluate the effect of the different components shaping a complex environmental enrichment over the expression of behavioral sensitization in mice previously exposed to toluene. For this purpose, 50 adolescent Swiss webster male mice were exposed to toluene vapors in a 27-liter cylindrical glass chamber (4000 ppm), 30 min/day, 4 weeks, following a previous reported protocol to induce behavioral sensitization. For the control group, 50 subjects were exposed to air (0 ppm of toluene). Subsequently, subjects were grouped and housed in cages during 4 weeks on 5 different environments (10 experimental and 10 control subjects per each environment): A) Standard Housing: five subjects housed in a cage with any physical element; B) Complete Environmental Enrichment: five subjects, 2 running wheels for voluntary exercise and 3 tunnels and toys; C) Exercise: five subjects and 3 running wheels for voluntary exercise; D) Cognitive Stimulation: five subjects and 5 tunnels and toys; E) Enrichment in Isolation: subjects individually caged with 1 running wheel and 1 toy. At the end of the housing protocols, animals were challenged with a single exposure of toluene (4000 ppm) during 30 min. The expression of behavioral sensitization was evaluated by counting the number of crossings performed in the lines-marked floor of the cylindrical glass chamber. Results showed that Standard Housing did not abolish behavioral sensitization at all, while Complete Enrichment avoided this behavior in animals with a previous history of toluene exposure. Both, environments for only Exercise and only Cognitive Stimulation reversed the behavioral sensitization, but in a lower extension than Complete EE; lineal analysis indicated a 79.7% of reversal effect attributed for Exercise and 35.6% of effect for Cognitive Stimulation. Conversely, EE in isolation was not able to block behavioral sensitization. We discuss that a complete environmental enrichment, including an enrichment for physical exercise and an enrichment for cognitive stimulation may reduce some addictive-like behaviors produced by inhalants, but in different levels. Physical exercise may be the main component provoking this effect. Also, social interaction may be an imperative element to get benefits induced by EE. Present findings from basic preclinical models can be used to advise on interventions for inhalant abusers based on physical activities and social relationships.