Repeated MDMA (“Ecstasy”) exposure in adolescent male rats alters temperature regulation, spontaneous motor activity, attention, and serotonin transporter binding

Abstract

Previous research in our laboratory found that repeated exposure of adolescent rats to 3,4-methylenedioxymethamphetamine (MDMA) impaired working memory and reduced anxiety. The present experiment extended these findings by investigating the physiological, behavioral, and neurotoxic effects of a modified MDMA treatment regimen. Male Sprague-Dawley rats received 5 mg/kg of MDMA hourly for a period of 4 hr on every fifth day from postnatal day 35-60. Acute effects of the MDMA treatment included hypothermia, serotonin syndrome behavior, and ejaculation. Body weight gain was attenuated by repeated drug administration. The animals completed anxiety and working memory tests beginning 4 days after the final MDMA dose. MDMA altered habituation to the open-field, increased locomotor activity in the elevated plus-maze, decreased attention in the novel object-recognition test, and reduced serotonin transporter binding in the neocortex. These results indicate that repeated exposure to a relatively moderate MDMA dose during adolescence produces later changes in behavior and neurochemistry.

Dissociation of the Neurochemical and Behavioral Toxicology of MDMA (‘Ecstasy’) by Citalopram

“…Because MDMA administration induces spontaneous ejaculation in rats (Bilsky et al, 1991;Piper et al, 2005, whereas citalopram and other SSRIs inhibit sexual responses (Rosen et al, 1999), the genitalia of the animals were inspected every 30 min following dosing and the presence of seminal discharge was noted. We determined the proportion of animals in each treatment group that ejaculated and, within this subset, we calculated the latency from first MDMA dose to the production of a seminal plug.…”

“…The number of days between dosing and behavioral testing is shown in parentheses for each test. Finally, the sequence of tests was similar to that used in previous work in our laboratory (Piper and Meyer, 2004;Piper et al, 2005) and was chosen to both maximize the detection of treatment effects and minimize carryover effects from one test to another.…”

“…This test was used to determine the effects of MDMA with and without citalopram on anxiety-like behavior (McGregor et al, 2003b;Piper et al, 2005). The apparatus consisted of a wooden hide box (24 Â 40 Â 15 cm), painted flat black with a hinged lid.…”

“…These tests were conducted in the aforementioned open-field to ensure habituation to the testing environment (Piper et al, 2005). The object-recognition test of working memory was conducted with two levels of difficulty.…”

“…Other measures of complex behavior have yielded variable results with respect to the influence of MDMA treatment. For example, some, but not all, studies have found that anxietylike behavior in the elevated plus-maze is sensitive to MDMA (Ho et al, 2004;Mechan et al, 2002;Piper and Meyer, 2004;Piper et al, 2005;Sumnall et al, 2004). Because MDMA is often described as a selective 5-HT neurotoxin (Cole and Sumnall, 2003;McCann and Ricaurte, 2004) that also produces long-lasting behavioral changes, investigators have commonly assumed that the 5-HT toxicity mediates such behavioral alterations.…”