Repeated administration of dextromethorphan (DXM) during adolescence produces greater acute locomotor stimulation and locomotor sensitization compared to adults, and only adolescent-treated rats show cross-sensitization to ketamine after abstinence. DXM also leads to increased perseverative errors in reversal learning exclusively in the adolescent group, indicating long-lasting cognitive flexibility deficits. These findings suggest that adolescent DXM use causes neuroadaptations that may contribute to addiction, though further work is needed to confirm the cognitive effects.
Repeated ketamine use during adolescence produces greater acute locomotor stimulation than in adulthood, but long-lasting behavioral sensitization—a marker of addiction-related neuroadaptation—persists only when exposure occurs in adults. In rats, 10 daily injections of 25 mg/kg ketamine caused immediate locomotor sensitization in both age groups, yet after 20 days of abstinence only adults retained this effect. No cross-sensitization to dextromethorphan was observed. Ketamine did not cause statistically significant cognitive deficits in spatial learning or object recognition in either age group, though adult-treated animals showed a trend toward spatial learning impairments. The findings suggest that adolescent and adult brains respond differently to repeated ketamine, with lasting neuroadaptations in adults that may contribute to addiction risk.