Ketamine sensitization: Influence of dose, environment, social isolation and treatment interval

Ketamine is a dissociative anesthetic first developed in the 1960s but is increasingly used at subanesthetic doses for both clinical and non-clinical purposes. There is evidence from human recreational users of compulsive use and addiction. Sensitization is an increase in an effect of a drug with repeated use that is thought to be important in the development of addiction. Research on psychomotor stimulants has shown the development of sensitization in laboratory animals to be modified by factors that influence addiction. In the current paper we describe four experiments on the development of sensitization in laboratory rats aimed at determining if ketamine sensitization is also influenced by factors thought to be important in addiction. Adult, male Sprague-Dawley rats received ketamine (5, 10, 20 or 50 mg/kg i.p.) for five or more days and the development of locomotor sensitization was followed. Experiment 1 examined the ability of low doses of ketamine to produce sensitization and found sensitization at 5, 10 and 20 mg/kg. Experiment 2 examined the influence of environmental context and found that ketamine sensitization (20 mg/kg) was greater when administration occurred in a novel environment (the experimental apparatus) than in home cages. Experiment 3 found that ketamine sensitization (20 mg/kg) did not occur when animals were housed in social isolation but occurred readily in pair-housed animals. Finally, Experiment 4 found that ketamine sensitization (20 or 50 mg/kg) was similar whether drug was administered daily or at 3-day intervals. Together, the results demonstrate that ketamine sensitization is robust and reliable, occurring under a variety of circumstances. Moreover, ketamine sensitization is influenced by factors that influence the development of addiction in humans. The current results may lead to a better understanding of ketamine abuse and addiction and may help inform clinical use of the drug.