Tolerance to the discriminative stimulus and reinforcing effects of ketamine

B. A. Rocha, A. S. Ward, Y. Egilmez, D. A. Lytle, M. W. Emmett-Oglesby

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23 Scopus citations

Abstract

In order to examine whether tolerance develops to the discriminative stimulus and reinforcing effects of ketamine, rats were trained either to discriminate ketamine (10 mg/kg) from saline or to self-administer ketamine (1.1 mg/kg/injection), and then treated with chronic ketamine (32 mg/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.

Original languageEnglish
Pages (from-to)160-168
Number of pages9
JournalBehavioural pharmacology
Volume7
Issue number2
DOIs
StatePublished - 1996

Keywords

  • Discriminative stimulus
  • Ketamine
  • Rat
  • Reinforcing effects
  • Self-administration
  • Tolerance

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