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

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.

Keywords: Adolescent rats; Cocaine; Conditioned activity; Ketamine; Locomotor activity; Preadolescent rats.

Fig. 1

Mean distance traveled scores (±SEM) of ketamine (0–40 mg/kg) treated female (upper graph) and male (lower graph) preadolescent rats on PD 21–25. The right panels represent total distance traveled collapsed across the five test days. Asterisks = Significant difference between the saline and 40 mg/kg ketamine group; Daggers = Significant difference between the saline and 20 mg/kg ketamine group; Double daggers = Significant difference between the saline and 10 mg/kg ketamine group.

Fig. 2

Mean distance traveled scores (±SEM) of female and male preadolescent rats across the 12 time blocks on PD 21 (upper graph) and PD 25 (lower graph). Asterisks = Significant difference between the saline and 40 mg/kg ketamine group; Daggers = Significant difference between the saline and 20 mg/kg ketamine group; Double daggers = Significant difference between the saline and 10 mg/kg ketamine group.

Fig. 3

Mean distance traveled scores (±SEM) of ketamine (0–40 mg/kg) treated female (upper graph) and male (lower graph) adolescent rats on PD 41–45. The right panels represent total distance traveled collapsed across the five test days. Asterisks = Significant difference between the saline and 40 mg/kg ketamine group; Daggers = Significant difference between the saline and 20 mg/kg ketamine group; Double daggers = Significant difference between female and male rats given the same dose of ketamine.

Fig. 4

Mean distance traveled scores (±SEM) of ketamine (0–40 mg/kg) treated female (upper graph) and male (lower graph) adolescent rats across the 12 time blocks on PD 41. Asterisks = Significant difference between the saline and 40 mg/kg ketamine group; Daggers = Significant difference between the saline and 20 mg/kg ketamine group.

Fig. 5

Mean distance traveled scores (±SEM) of ketamine (0–40 mg/kg) treated female (upper graph) and male (lower graph) adolescent rats across the 12 time blocks on PD 45. Asterisks = Significant difference between the saline and 40 mg/kg ketamine group; Daggers = Significant difference between the saline and 20 mg/kg ketamine group.

Fig. 6

Mean test day (PD 25) distance traveled scores (±SEM) of preadolescent rats from the 10 mg/kg (upper graph) and 40 mg/kg (lower graph) ketamine groups. Asterisks = Significantly different from the saline control group in the same drug condition. Daggers = Significantly different from the paired group in the same drug condition.

Fig. 7

Mean test day (PD 45) distance traveled scores (±SEM) of female and male adolescent rats from the 10 mg/kg (upper graph) and 40 mg/kg (lower graph) ketamine groups. Asterisks = Significantly different from the saline control group in the same drug condition. Daggers = Significantly different from the paired group in the same drug condition.