Repeated toluene inhalation in male and female adolescent rats induces persistent drug preference and impairs cognitive and social behavior

Adolescent inhalant use is an understudied and undertreated disorder, particularly in females. Chronic exposure to inhalants, like toluene, can have long-lasting effects on behavior. However, most animal studies lack the incorporation of both sexes and do not focus on the abstinence period. We assessed the behavioral effects during prolonged abstinence following repeated toluene inhalation in adolescent male and female rats. We repeatedly exposed adolescent male and female Sprague Dawley rats to toluene vapor (1500 or 3000 ppm) for 6 days using the conditioned place preference (CPP) procedure. We tested drug-associated context preference, locomotion, anxiety-like behavior, object memory, social preference, and cognitive flexibility across 22 days of abstinence. In females, 3000 ppm toluene increased CPP on days 8 and 22 of abstinence but this effect did not reach significance in males. Instead, males showed a significant increase in locomotion on days 7 and 21. Toluene also impaired social novelty preference and reversal learning during long-term abstinence, but not anxiety-like behavior or object recognition memory. Our rodent findings suggest that female inhalant users may show persistent drug preference during abstinence following chronic use. Furthermore, prolonged cognitive and social deficits should be addressed in treatment programs for adolescents.