Differential effects of methamphetamine and cocaine on conditioned place preference and locomotor activity in adult and adolescent male rats

Abstract

Human and animal laboratory studies show that adolescents and adults respond differently to drugs and that drug administration during adolescence leads to different behavioral effects than during adulthood. Although there are a number of studies on the effects of cocaine, little is known about the effects of methamphetamine in adolescent vs adult rats. In the present study, sensitivity to the conditioned reward of multiple doses of methamphetamine or cocaine was evaluated in male adolescent (PND 34) and adult (PND 66) rats using a conditioned place preference (CPP) paradigm. In addition, the locomotor-activating effects of methamphetamine were determined across a 5-day period of administration. After 3 days of training with cocaine, both adolescent and adult male rats developed CPP to cocaine, however, the dose-effect curve for cocaine CPP was shifted to the left in adolescent compared to adult rats. In contrast to the development of CPP to cocaine in both groups after 3 days of conditioning, methamphetamine CPP occurred only in adolescent, and not in adult rats. After 5 days of training, however, both adolescent and adult rats exhibited identical responses to multiple doses of methamphetamine and a significant CPP was observed in both groups. Daily administration of methamphetamine increased locomotor activity in both adolescent and adult rats, with a greater effect seen in the adults. In neither group, was there evidence of a significant sensitization to the locomotor-activating effects of methamphetamine. These data show that adolescents are more sensitive to psychostimulant reward and thus to the conditioned rewarding properties of cocaine or methamphetamine than adults. A better understanding of this difference may lead to age-specific preventions and treatments for psychostimulant abuse.

Fig. 1

Locomotor activity in (A) periadolescent male (PAM) and (B) adult male (ADM) rats in response to VEH, 0.125 mg/kg or 0.5 mg/kg methamphetamine. The data are expressed as mean ± SEM of distance traveled in 60 min test sessions across 5 days of treatment and testing. The dose of 0.5 mg/kg methamphetamine significantly increased activity over saline levels in both groups (P ≤ 0.05), with a greater effect in adults, and the effect of this dose was not significantly altered across days. MA = methamphetamine

Fig. 2

Methamphetamine CPP in response to training for (A) 3 days or (B) 5 days. Data are presented as the amount of time spent in the methamphetamine-paired chamber during the post-test minus time spent in the methamphetamine-paired chamber during the pretest. A value of 0 represents no change. A positive value represents an increase in preference for the methamphetamine-paired side and a negative value represents an increased preference for the saline-paired side. After 3 days of training (A), both 0.125 mg/kg and 0.5 mg/kg methamphetamine produced significant increases in the amount of time spent in the methamphetamine-paired side of the chamber during the post-test in adolescent rats, but none of the doses led to a significant CPP in the adult rats. After 5 days of training (B), either 0.125 mg/kg, 0.5 mg/kg or 1.0 mg/kg methamphetamine led to a significant CPP in both adolescent and adult rats. A dose of 0.06 mg/kg methamphetamine did not produce a significant CPP after either training paradigm. N = 8–10 per group. Doses in the x-axis are shown on a log scale. *significantly different from 0 (P < 0.05). MA = methamphetamine

Fig. 3

Methamphetamine CPP in adult rats in response to training with 0.5 mg/kg. for: 3 days with a post-test conducted one day after the last training session (3D + 1, n=10), 3 days with a 3 day delay before testing (3D + 3, n=10), or 5 days with a 3 day delay before testing (5D + 3, n=8). Data are presented as the amount of time spent in the methamphetamine-paired chamber during the post-test minus time spent in the methamphetamine-paired chamber during the pretest. Only the five-day training paradigm led to a significant change in preference over the pretest. *significantly different from 0 (P < 0.05). MA = methamphetamine

Fig. 4

Cocaine conditioned place preference. Adolescent and adult rats were trained with cocaine (3–20 mg/kg/day) and saline for three days. Data are presented as time spent in the cocaine-paired chamber during the post-test (day 5) minus time spent in cocaine-paired chamber during the pretest (day 1, prior to training) expressed as seconds. The 0 line represents no preference. A positive value represents an increase in preference for the cocaine-paired side and a negative value represents an increased preference for the saline-paired side. N = 8–12 animals per group. Doses in the x-axis are shown on a log scale. *significant difference from 0 (P < 0.05).