Ketamine self-administration in the rat: evidence for a critical role of setting

The abuse of ketamine has been reported to be on the rise over the past 15 years, but its abuse appears to be limited almost exclusively to the context of music and dance settings, indicating a major role of context in modulating its reinforcing effects. We have previously reported that amphetamine, cocaine, and heroin self-administration (SA) in the rat are differentially influenced by the setting in which testing takes place. The aim of the present study is to extend this pre-clinical model to ketamine. Independent groups of rats with intravenous catheters were given the possibility to self-administer different doses of ketamine (125, 250, and 500 mu g/kg per infusion) under two environmental conditions. Some animals were housed in the SA chambers (resident rats) whereas other rats were transported to the SA chambers only for the test sessions (non-resident rats). After training, within-subject dose effect curves (125, 250, 500, and 1,000 mu g/kg per infusion) and break-point (during a progressive ratio session) were calculated. Non-resident rats readily acquired ketamine self-administration. In contrast, resident rats self-administered only the highest dose of ketamine (500 mu g/kg), but still four times less than non-resident rats (11.0 +/- 6.0 vs 44.4 +/- 5.2 infusions during the last training session). No significant differences in break-point were found during the progressive ratio session. The present study confirms at a preclinical level the importance of setting for ketamine SA and further validates a previously described animal model of drug-environment interaction.