Effects of Dissociative Exposure in Adolescence on Behavior in Adulthood

Ketamine and dextromethorphan belong to the drug class known as dissociatives. They produce several behavioral effects, including dissociation from self and disruptions in learning and memory. Initiation of dissociative use is often in adolescence, and little is known about the long-term effects of these drugs when their use begins in this developmental period. In the present research, groups of adolescent and adult male rats were repeatedly treated with ketamine or dextromethorphan and assessed for locomotor sensitization (i.e., increased locomotor behavior following repeated administration) or cognitive deficits in two distinct learning tasks: spatial learning and object recognition. To understand the long-term effects of these drugs, sensitization was assessed immediately after the final injection and following an abstinence period of 20 days; cognitive deficits were assessed only after the 20 day abstinence period. Regardless of age, 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. In contrast, only adolescent animals treated with dextromethorphan demonstrated sensitization immediately after the final injection, while both groups displayed sensitization after abstinence. Ketamine and dextromethorphan failed to produce statistically significant cognitive deficits in either age group. However, both drug-treated adult groups showed a trend towards increased deficits in spatial learning. These data indicate that use of ketamine and dextromethorphan can produce long-lasting neuroadaptations that may contribute to addiction, as well as lead to memory deficits in adult users. Together, the results suggest that caution be taken when using these drugs and further research is necessary to understand their mechanisms of action.