• B.A. Rocha, A.S. Ward, Y. Egilmez, D.A. Lytle, and M.W. Emmett-Oglesby.
• Department of Pharmacology, University of North Texas HSC, 3500 Camp Bowie Blvd., Fort Worth, TX 76107-2699, USA.
• Behav Pharmacol. 1996 Mar 1; 7 (2): 160-168.

AbstractIn order to examine whether tolerance develops to the discriminative stimulus and reinforcing effects of ketamine, rats were trained either to discriminate ketamine (10mg/kg) from saline or to self-administer ketamine (1.1mg/kg/injection), and then treated with chronic ketamine (32mg/kg), administered i.p. every 8 hours for 7 days. No shift in the dose-response curve for either paradigm was obtained following this chronic regimen. However, following a 2-week rest period in which animals had no exposure to ketamine, the dose-response curve was shifted two-fold to the left, indicating increased sensitivity to the drug. Reinstatement of training shifted the dose-response curve back to the right in both paradigms. These results suggest that tolerance to the discriminative stimulus and reinforcing effects of ketamine develops during training. Examination of the self-administration training data support this assumption, since inter-reinforcer time decreases, reflecting an increase in ketamine intake over training sessions.

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