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.

Transient D1Dopamine Receptor Expression on Prefrontal Cortex Projection Neurons: Relationship to Enhanced Motivational Salience of Drug Cues in Adolescence

“…For example, handling is one such variable to consider. Handling history may account for enhanced preferences for lower doses of cocaine, as suggested by comparisons across several studies with and without previous handling (Andersen et al, 2002b;Aberg et al, 2007;Brenhouse and Andersen, 2008). Together, age-related differences in the place-conditioning effects of cocaine reported here are consistent with an enhanced sensitivity to these effects in adolescent rats, when examining male animals in an unbiased place-conditioning paradigm.…”

Delayed extinction and stronger reinstatement of cocaine conditioned place preference in adolescent rats, compared to adults.

“…Third, prior handling seems to influence the degree of place conditioning. For example, adolescents at ages similar to those used in the present study failed to show preferences for environments associated with 10 mg/kg of cocaine (Aberg et al, 2007).…”

“…For example, nicotine and alcohol elicit greater place preferences in adolescents relative to adult rats (Belluzzi, Lee, Oliff, & Leslie, 2004;Philpot, Badanich, & Kirstein, 2003;Vastola, Douglas, Varlinskaya, & Spear, 2002). However, other place conditioning studies using cocaine (Aberg, Wade, Wall, & Izenwasser, 2007;Campbell, Wood, & Spear, 2000) did not report greater preferences in adolescents. Experimental differences may account for these disparities.…”

The effects of concurrent administration of (±)3,4-Methylenedioxymethamphetamine and cocaine on conditioned place preference in the adult male rat

“…Interestingly, a purportedly neurotoxic dose of MDMA (20 mg/kg, s.c.) administered prior to MDMA CPP testing significantly decreased conditioning at lower doses of the test dose, but not at higher doses of the test dose (Schechter, 1991). More directly related to the rationale that formed the basis for the present investigation, a recent report by Aberg et al (2007) showed that for adult rats cocaine-induced (10 mg/kg) CPP was diminished by MDMA administered five days prior to CPP training. However, in this study only a single dose of cocaine was tested and there was no attempt to determine the effects of cojoint exposure, which as noted above is the more likely pattern of exposure among young adults.…”