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Effects of ketamine on the unconditioned and conditioned locomotor activity of preadolescent and adolescent rats: impact of age, sex, and drug dose

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Abstract

Rationale

Ketamine is used by preadolescent and adolescent humans for licit and illicit purposes.

Objective

The goal of the present study was to determine the effects of acute and repeated ketamine treatment on the unconditioned behaviors and conditioned locomotor activity of preadolescent and adolescent rats.

Methods

To assess unconditioned behaviors, female and male rats were injected with ketamine (5–40 mg/kg), and distance traveled was measured on postnatal day (PD) 21–25 or PD 41–45. To assess conditioned activity, male and female rats were injected with saline or ketamine in either a novel test chamber or the home cage on PD 21–24 or PD 41–44. One day later, rats were injected with saline and conditioned activity was assessed.

Results

Ketamine produced a dose-dependent increase in the locomotor activity of preadolescent and adolescent rats. Preadolescent rats did not exhibit sex differences, but ketamine-induced locomotor activity was substantially stronger in adolescent females than males. Repeated ketamine treatment neither caused a day-dependent increase in locomotor activity nor produced conditioned activity in preadolescent or adolescent rats.

Conclusions

The activity-enhancing effects of ketamine are consistent with the actions of an indirect dopamine agonist, while the inability of ketamine to induce conditioned activity is unlike what is observed after repeated cocaine or amphetamine treatment. This dichotomy could be due to ketamine’s ability to both enhance DA neurotransmission and antagonize N-methyl-D-aspartate (NMDA) receptors. Additional research will be necessary to parse out the relative contributions of DA and NMDA system functioning when assessing the behavioral effects of ketamine during early ontogeny.

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  1. Department of Psychology, California State University, 5500 University Parkway, San Bernardino, CA, 92407, USA

    Sanders A. McDougall, Andrea E. Moran, Timothy J. Baum, Matthew G. Apodaca & Vanessa Real

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  1. Sanders A. McDougall
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  2. Andrea E. Moran
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  3. Timothy J. Baum
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Correspondence to Sanders A. McDougall.

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This research was supported by NIGMS training grant GM083883 (TJB and VR) and NIDA training grant DA033877 (AEM).

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The authors declare that they have no conflict of interest.

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McDougall, S.A., Moran, A.E., Baum, T.J. et al. Effects of ketamine on the unconditioned and conditioned locomotor activity of preadolescent and adolescent rats: impact of age, sex, and drug dose. Psychopharmacology 234, 2683–2696 (2017). https://doi.org/10.1007/s00213-017-4660-3

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