Long-lasting effects of repeated ketamine administration in adult and adolescent rats.

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.

Study at a glance

Abstract

Initiation of ketamine use often occurs in adolescence, yet little is known about long-term consequences when use begins in this developmental period. The current experiments were designed to examine the effects of repeated exposure to ketamine in adolescence on behavior in adulthood. We examined locomotor activity, as well as cognitive function, in animals that received repeated administration of ketamine. Groups of adolescent and adult male rats were treated with ketamine (25 mg/kg) once daily for 10 days. Locomotor activity was assessed following the first injection, following 10 days of injection, and following 20 days of abstinence. Acute locomotor effects and locomotor sensitization were compared in adolescents and adults; cross-sensitization to dextromethorphan, another dissociative with abusive potential, was also examined. In a separate group of animals cognitive deficits were assessed following the 20 day abstinence period in spatial learning and novel object recognition tasks. The locomotor stimulant effect of ketamine was much greater in adolescents than adults. Animals that were repeatedly administered ketamine demonstrated locomotor sensitization immediately after the final injection. However, sensitization only persisted after the abstinence period in animals treated as adults. No cross-sensitization to dextromethorphan was evident. Ketamine failed to produce statistically significant cognitive deficits in either age group, although drug-treated adults showed a trend towards deficits in spatial learning. Repeated use of ketamine produces long-lasting neuroadaptations that may contribute to addiction. Mild lasting memory deficits may occur in adults, although further work is necessary to confirm these findings. The results extend the understanding of potential long-term consequences of ketamine use in adolescents and adults.