Adolescent MDMA Exposure Diminishes the Physiological, Behavioral, and Neurotoxic Consequences of a Subsequent Methamphetamine Binge

Abstract

Previous research showed that repeated adolescent ±3,4methylenedioxymethamphetamine (MDMA) treatments diminished the temperature dysregulation, hypoactivity/"hangover" effect, and serotonin transporter reductions caused by a subsequent MDMA binge. This study evaluated whether MDMA would confer crosstolerance against a methamphetamine (METH) binge. Rats received MDMA (10 mg/kg × 2) every fifth day from postnatal day (PD) 35 to PD 60 followed by a low or high METH binge (4 or 8 mg/kg × 4) on PD 67. Adolescent MDMA preexposure diminished, but did not prevent, the METH-induced increase in core body temperature. Adolescent MDMA exposure conferred resistance to the METHinduced hypoactivity in rearing behavior on PD 68. The high-dose METH binge caused reductions in [ 3 H]citalopram binding to the serotonin transporter in the frontal cortex, parietal cortex, and hippocampus which were attenuated by adolescent MDMA. Similarly, adolescent MDMA blunted the METH binge-induced decrease in striatal [ 3 H]WIN35,428 binding to the dopamine transporter. Together, these findings are supportive of a preconditioning effect between the two different substituted amphetamines.