Subchronic anesthetic ketamine injections in rats impair choice reversal learning, but have no effect on reinforcer devaluation

Previous exposure to a variety of drugs of abuse has been shown to cause long-term impairments in reversal learning and reinforcer devaluation tasks. However, there is mixed evidence in the literature for a long-term effect of ketamine exposure on reversal learning and the long-term effect of ketamine exposure on devaluation is not known. We determined whether repeated injections of an anesthetic dose of ketamine would lead to impairments in choice reversal learning after discrimination learning or impairments in reinforcer devaluation. In two experiments, rats received three injections once-daily of ketamine (100mg/kg, intraperitoneally) or saline and then began behavioral training 19 days later so that the key reversal learning and devaluation tests would occur about 1 month after the final ketamine injection. This ketamine exposure regimen did not impair learning in our discrimination task, but led to an increase in perseverative errors in reversal learning. However, the same ketamine exposure regimen (or injections of a lower 50mg/kg dose) had no effect on behavior in the devaluation task. The behavioral patterns observed suggest possible neural mechanisms for the effects of ketamine, but future neurobiological investigations will be needed to isolate these mechanisms.