Biol Psychiatry. 2007 Jun 11; Increased Response to Ketamine Following Treatment at Long Intervals: Implications for Intermittent Use. Trujillo KA, Zamora JJ, Warmoth KP. Department of Psychology and Office for Biomedical Research and Training, California State University San Marcos, San Marcos, California. [b]BACKGROUND:[/b] Ketamine has been used for many years as a dissociative anesthetic; however, there is evidence of increasing abuse, especially at dance clubs and raves. In addition, there is increasing interest in the use of subanesthetic doses of ketamine for the treatment of pain and depression, as well as for clinical research on schizophrenia. Despite growing use, relatively little is known about the consequences of repeated administration of low doses of ketamine. [b]METHODS:[/b] To determine the changes in response to repeated administration, ketamine (20 mg/kg or 50 mg/kg intraperitoneal [IP]) was administered once weekly to laboratory rats and the locomotor response was assessed following each injection. [b]RESULTS:[/b] Repeated administration of ketamine led to an escalation in the stimulant effects of the drug, characteristic of behavioral sensitization. The development of sensitization was greater when ketamine was repeatedly administered in the presence of distinct environmental cues. [b]CONCLUSIONS:[/b] Intermittent administration of ketamine at weekly intervals leads to the development of locomotor sensitization. These results suggest caution in the repeated use of ketamine for recreational or clinical purposes.