Mdma and Methamphetamine: An Investigation of a Neurochemical and Behavioral Cross-Tolerance in the Rat
Christina S. Henderson
Scholarworks (University of Massachusetts Amherst) August 15, 2023 DOI: 10.7275/835043 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experimental animal study Peer reviewed |
|---|---|
| Population | Adolescent male Sprague-Dawley rats |
| Interventions | MDMA Methamphetamine |
| Dose | MDMA 10 mg/kg x 2 (4-h interdose interval); METH 4 or 8 mg/kg x 4 (2-h interdose interval) |
| Duration | MDMA pretreatment every fifth day from postnatal day 35 through 60; METH challenge on postnatal day 67; activity measured 1 day after binge; transporter binding analyzed at postnatal day 74 |
| Measures | radioligand binding for serotonin transporter (SERT) and dopamine transporter (DAT), activity measurement |
| Topics | MDMA |
| Key findings | Intermittent adolescent MDMA pretreatment fully or partially protected against methamphetamine-induced serotonin transporter deficits, depending on brain region, but did not protect against striatal dopamine transporter loss. The authors suggest the neuroprotective effects are confined to the serotonergic system, possibly reflecting selective upregulation of antioxidant mechanisms. |
Abstract
We previously found that intermittent administration of 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) to adolescent male rats protected against the behavioral and serotonergic neurotoxic effects of a subsequent MDMA binge. Similar results have been reported for the dopamine (DA) neurotoxin methamphetamine (METH). The present study tested the hypothesis that intermittent adolescent MDMA exposure would protect against the DA neurotoxic effects of a METH binge. Male Sprague-Dawley rats were injected s.c. with MDMA (10 mg/kg x 2; 4-h interdose interval) or saline every fifth day from postnatal day (PD) 35 through PD 60. The animals were then challenged with either a low- or high-dose METH binge (4 or 8 mg/kg x 4; 2- h interdose interval) or saline on PD 67. Activity was measured 1 day after the binge, and regional serotonin transporter (SERT) and dopamine transporter (DAT) expression were analyzed at PD 74 by radioligand binding. All animals treated with METH on the challenge day became hyperthermic, independent of pretreatment conditions. Both MDMA-pretreated and drug-naïve rats also showed a dose-dependent hypoactivity 24 h after the first dose of the METH binge. The SERT binding results indicated that adolescent pretreatment with MDMA provided full or partial protection (depending on the brain region) against the serotonergic deficits produced by METH in previously drug-naïve animals. In contrast, MDMA pretreatment failed to protect against METH-induced decreases in striatal DAT binding. These results suggest that the neuroprotective 2 effects of adolescent MDMA pretreatment are confined to the serotonergic system, possibly reflecting a selective upregulation of antioxidant mechanisms in that system.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.