Examination of ketamine-induced deficits in sensorimotor gating and spatial learning.

Subanesthetic administration of the NMDA receptor antagonist ketamine has been suggested to have utility in several therapeutic domains; however, its recreational use has exceeded its therapeutic applications. Ketamine has been utilized to investigate NMDA receptor-mediated learning and memory and to model disorders such as schizophrenia. The utility of ketamine in relation to schizophrenia is based on a proposed mechanism of the disorder being associated with reduced NMDA receptor function within a subset of GABAergic neurons. The examination of ketamine with relevance to the above topics has produced valuable data; however, there exists a great deal of variability in the literature regarding dosage and timing of administration to examine ketamine-induced deficits. In the below experiments we sought to identify the minimal subanesthetic dosage and schedule of ketamine administrations that would produce behavioral deficits in multiple tasks with relevance to the above investigations. We evaluated sensorimotor gating as well as spatial learning and memory in the Morris water task utilizing different doses of ketamine. Our data indicate that an 8 mg/kg subcutaneous dose of ketamine was the minimal dose to produce impairments in both sensorimotor gating and spatial learning.