Positive reinforcement and c‐Fos expression following abuse‐like thinner inhalation in mice: Behavioural and immunohistochemical assessment

Thinners are organic solvents widely used in industrial applications, but they have also been subject to abuse by inhalation for their psychoactive and rewarding properties. In spite of the prevalence of inhalant abuse, the addictive potential and pathways mediating their reinforcing effects are not yet fully understood and thus still subject of further investigations. Here, we assessed in mice the locomotor activity and the ability of paint thinner to reinforce the conditioning in the place preference paradigm following acute (1 day), subchronic (6 weeks) and chronic (12 weeks) exposures to 300 and 600 ppm of thinner vapor. While locomotor activity was unaffected by the different thinner treatments, a positive conditioned place preference to inhaled thinner was found upon subchronic and chronic exposures. To investigate the activated brain structures underlying such behavioural changes, we analyzed the distribution of c‐Fos immunoreactivity, a marker for neuronal activation, following acute and repeated exposures to 600 ppm of thinner. Notably, thinner exposure increased the number of c‐Fos immunoreactive neurons with increasing duration of exposure in the majority of structures examined; including those typically involved in the processing of rewarding or emotionally stimuli (e.g., ventral tegmental area, core and shell of nucleus accumbens, amygdala, bed nucleus of the stria terminalis, and cingulate cortex), and olfactory stimuli (e.g., piriform cortex and olfactory tubercle). Moreover, prolonged, but not acute thinner inhalation significantly increased c‐Fos immunoreactivity in all hippocampal subregions. Taken together, the expanded distribution of thinner‐induced c‐Fos expression may underlie the observed positive reinforcement upon long‐term thinner inhalation.