Dr. Rohani B. Cena-Navarro
University of the Philippines Manila

The use of solvents (toluene) is a worldwide problem and is prevalent especially in Filipino street boys and girls. Despite years of research, important questions have not been addressed and treatments have not been successful. Studies on the effects of toluene on female and social behavior are also unknown. We recently reported that repeated toluene inhalation at 3000 ppm increased conditioned place preference (CPP) in females and impaired social novelty preference during the abstinence period (Asis et al., 2024).

We now attempt to restore these behavioral deficits using low-cost pharmacological (N-acetylcysteine) and behavioral (exercise) treatments. NAC and exercise are two treatments that have been shown to decrease drug-seeking in other substance abuse but have not been tested in toluene.

We repeatedly exposed adolescent male and female Sprague Dawley rats to toluene vapor (3000 ppm) for six days using the CPP paradigm. During an eight-day abstinence period, animals received either N-acetylcysteine (100 mg/kg, intraperitoneally) or daily voluntary wheel running (4 hours/day) as low-cost interventions. We assessed drug-associated context preference, locomotor activity, and social preference throughout the abstinence period. 

Here, we report that daily NAC injections (100 mg/kg I.P.) during abstinence (D1 to D8) significantly decreased the CPP score (two-way RM ANOVA main effect of time: p=0.001) in toluene-exposed males. In toluene-exposed females that received treatments via drinking water, NAC significantly decreased the CPP score (two-way RM ANOVA main effect of time: p=0.007). Similar to NAC, exercise using daily voluntary wheel running (4h/d) during abstinence (D1 to D8) significantly reduced CPP score in toluene-exposed rats (two-way RM ANOVA time × group interaction: p=0.037). NAC and exercise also restored social novelty preference in females (NAC: two-way RM ANOVA main effect of time p=0.026; Exercise: two-way RM ANOVA main effect of phase: p=0.022). Lastly, exercise (but not NAC) reduced locomotion in females (t-test p=0.006), but not in males (t-test p=0.156).

Overall, NAC and exercise treatment can reverse the toluene-induced behavioral deficits during the abstinence period. We are now performing cFos immunofluorescence to determine the extent of treatments in reversing the brain back to its pre-addiction state.