Effect of MDMA (ecstasy) on activity and cocaine conditioned place preference in adult and adolescent rats
Introduction
MDMA (ecstasy) is a drug that is typically used by teenagers and young adults in bars and clubs. The National Survey on Drug Use and Health has estimated that about 2.1 million people over 12 years of age reported having used ecstasy in the past year, with the majority being young adults [25]. In addition, MDMA users were more likely to use other drugs compared to non-MDMA users, with 90% of MDMA users and only 13.8% of non-MDMA users reporting having used other illicit drugs. Specifically, cocaine was reported as being used by 43.8% of MDMA users and 2.0% of non-MDMA users [25].
In adult rats, MDMA increases locomotor activity and at high doses produces behaviors indicative of a serotonin syndrome (e.g. forepaw treading, low body posture) (see [15] for review). Sensitization occurs to the locomotor-activating effects of MDMA after repeated administration [28]. The increased locomotor activity is seen with low doses (3 or 4 mg/kg) and an even greater effect is seen with higher doses (8 or 12 mg/kg) [16]. There are conflicting results from studies of the reinforcing effects of MDMA with some studies showing a conditioned place preference (CPP) after s.c. [6], [20] or i.c.v. [7] administration of MDMA. Other studies, however, have shown that there is no significant CPP to MDMA in group housed rats, but rather that it occurs only in isolated rats [22]. Repeated treatment with MDMA in adult rats has been reported to facilitate the subsequent acquisition of cocaine self-administration (Fletcher et al., 2001), suggesting that there are crossover effects between MDMA and cocaine, while other studies show no crossover effects between MDMA and amphetamine or methylphenidate [23].
Previous experiments have shown that adult and adolescent rats have different neurochemical adaptations in response to MDMA, where the adolescent rats seem to be less vulnerable to the toxic effects. Experiments in adult rats have shown that either a repeated low dose (4 mg/kg) for 4 days [26], or one high dose (20 mg/kg) [21], caused significant decreases in serotonin concentrations in selected brain regions. In adolescent rats on the other hand, experiments have revealed that repeated administration of MDMA (7.5 mg/kg) twice daily for 3 days starting on PND 39 [14], or one dose of MDMA (20 mg/kg) on PND 14 or 21 [4] did not significantly alter the serotonin concentration.
Since MDMA is a drug predominately used by young adults and teenagers, it is important to investigate what effect this drug might have during this stage of development. Rats used in this study were either adolescents aged postnatal day (PND) 33 or adults aged PND 60 at the start of the experiments. In the rat, the periadolescent period, which is the period of early adolescence, takes place around PND 28-42 [29].
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Subjects
The animals used in this study were maintained and the studies were conducted in accordance with the guidelines of the Guide for Care and Use of Laboratory Animals, National Research Council, Department of Health, Education and Welfare, NIH Publication 85-23, revised 1996. Sprague-Dawley male adolescent and adult rats (Charles River, Wilmington, MA) were used in all studies. Rats were housed two per cage in a temperature and humidity-controlled environment under a 12 h light/dark cycle. Food
Locomotor activity
A dose of 2.0 mg/kg MDMA stimulated activity in both adult and adolescent rats on each day of testing, although the activity levels were higher in the adult rats (Fig. 1). There was a significant treatment effect overall (F(1,112) = 43.55, p = 0.0001), and post-hoc tests showed that there was a significant difference between MDMA and vehicle treatment in both adults (p = 0.0001) and adolescents (p = 0.01). The time-course of the locomotor-stimulating effects of this dose of MDMA within the 60 min
Locomotor activity
The data from the locomotor activity studies showed that a dose of 2 mg/kg of MDMA stimulated activity in both adult and adolescent rats, although the activity levels in response to the MDMA were higher in adult rats than in adolescents. The time-course of the activating effects of this dose of MDMA was different in adults and adolescent rats with a significant increase in activity observed after 5 min in adult rats compared to 15–20 min in adolescents. Adult rats were sensitized to the
Acknowledgments
This work was supported by the National Institute on Drug Abuse grant DA 15119.
Conflict of Interest
None of the authors have any conflicts of interest related to this manuscript.
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