Effect of MDMA (ecstasy) on activity and cocaine conditioned place preference in adult and adolescent rats

Abstract

MDMA (ecstasy) is a drug commonly used in adolescence, and many users of MDMA also use other illicit drugs. It is not known whether MDMA during adolescence alters subsequent responses to cocaine differently than in adults. This study examined the effects of MDMA in adolescent and adult rats on cocaine conditioned reward. At the start of these experiments, adolescent rats were at postnatal day (PND) 33 and adult rats at PND 60. Each rat was treated for 7 days with MDMA (2 or 5 mg/kg/day or vehicle) and locomotor activity was measured. Five days later cocaine conditioned place preference (CPP) was begun. Rats were trained for 3 days, in the morning with saline and in the afternoon with 10 mg/kg cocaine in 30 min sessions, and tested on the fourth day. MDMA stimulated activity in both age groups, but with a greater effect in the adult rats. Sensitization to the locomotor-stimulant effects of the lower dose of MDMA occurred in adult rats and in both groups to the higher dose. Cocaine did not produce a CPP in vehicle-treated adolescent rats, but a significant CPP was observed subsequent to treatment with MDMA. In contrast, cocaine-induced CPP was diminished after MDMA in adult rats. These effects were still evident 2 weeks later upon retest. Thus, under the present conditions, MDMA increased cocaine conditioned reward in adolescent and decreased it in adult rats. These findings suggest that exposure to MDMA during this critical developmental period may carry a greater risk than during adulthood and that male adolescents may be particularly vulnerable to the risk of stimulant abuse after use of MDMA.

Fig. 1

Daily locomotor activity in adolescent male (PAM, left panel) and adult male (ADM, right panel) rats in response to 2.0 mg/kg/day MDMA or vehicle (saline). Data show the amount of horizontal activity in a 60 min test session, which was begun 15 min after injection of MDMA or saline. Rats were injected daily for 7 days and locomotor activity was tested on days 1,2, 6, and 7. *significant difference from vehicle (p ≤ 0.05). #significant difference from day 1 (p ≤ 0.05).

Fig. 2

Time courses of locomotor activity on each of the test days in both adolescent male (PAM, left panels) and adult male (ADM, right panels) rats after 2.0 mg/kg MDMA or vehicle. These data show the amount of horizontal activity per 5 min period over a 60 min test session on each of the test days.

Fig. 3

Daily locomotor activity in adolescent male (PAM, left panel) and adult male (ADM, right panel) rats in response to 5.0 mg/kg/day MDMA or vehicle (saline). Data show the amount of horizontal activity in a 60 min test session, which was begun 15 min after injection of MDMA or saline. Rats were injected daily for 7 days and locomotor activity was tested on days 1,2, 6, and 7. *significant difference from vehicle (p ≤ 0.05). #significant difference from day 1 (p ≤ 0.05).

Fig. 4

Time courses of locomotor activity on each of the test days in both adolescent male (PAM, left panels) and adult male (ADM, right panels) rats after 5.0 mg/kg MDMA or vehicle. These data show the amount of horizontal activity per 5 min period over a 60 min test session on each of the test days. At this dose, the time course of the effect of MDMA is the same in the adult and adolescent rats after several days of treatment, however on day 2 the onset of locomotor stimulation occurs sooner in the adolescent rats.

Fig. 5

Cocaine conditioned place preference in adolescent male (PAM) and adult male (ADM) rats. Rats were trained with cocaine (10 mg/kg/day) and saline from days 12–14 of the experiment (beginning 5 days after last treatment with vehicle, 2.0 mg/kg MDMA or 5.0 mg/kg MDMA). On day 15, preference was tested by allowing rats to have access to both sides of the chamber. The time spent on each side (secs) was recorded. Data are presented as preference values (time spent in cocaine-paired chamber minus time spent in saline-paired chamber expressed as seconds). The 0 line represents no preference. *significant difference from 0. #significant difference from vehicle pretreatment.

Fig. 6

Retest of cocaine conditioned place preference in adolescent male (PAM) and adult male (ADM) rats 2 weeks after first test. Rats were trained with cocaine (10 mg/kg/day) and saline from days 12–14 of the experiment (beginning 5 days after last treatment with vehicle or 5.0 mg/kg MDMA). On day 29, preference was tested by allowing rats to have access to both sides of the chamber. The time spent on each side (secs) was recorded. Data are presented as preference values (time spent in cocaine-paired chamber minus time spent in saline-paired chamber expressed as seconds). The 0 line represents no preference. *significant difference from 0. #significant difference from vehicle pretreatment.