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Repeated intermittent methylenedioxymethamphetamine exposure protects against the behavioral and neurotoxic, but not hyperthermic, effects of an MDMA binge in adult rats.
Synapse 2010; 64(6):421-31S

Abstract

We have recently shown that chronic intermittent exposure of adolescent rats to 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) completely blocks the reduction in serotonin transporter (SERT) binding and the hypoactivity seen following a subsequent MDMA binge treatment. The present study determined whether a similar neuroprotective effect also occurs in rats given the same intermittent MDMA exposure in adulthood. Adult male Sprague-Dawley rats were given either MDMA (10 mg/kg x 2) or saline, every fifth day, from postnatal day (PD) 60 to PD 85. The MDMA-induced latency until seminal plug production was reduced over the course of intermittent treatments. After a 1-week wash-out period, animals received either a low- or high-dose MDMA binge (2.5 or 5.0 mg/kg x 4). Core body temperature was measured during and after the binge to determine the effects of MDMA pretreatment on MDMA-induced hyperthermia. Spontaneous motor activity was determined the next day, and cortical and hippocampal samples were collected at 1 week postbinge to measure serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations as well as [3H]citalopram binding to SERT. Hyperthermia occurred more rapidly and seminal discharge was more common in the MDMA-pretreated group compared to the MDMA-naïve group in animals given the low-dose binge. MDMA preexposure protected animals from the reductions in cortical 5-HT levels and SERT binding produced by the high-dose binge and blocked the postbinge hypoactivity. These findings indicate that chronic, intermittent MDMA exposure in adulthood induces neuroprotective effects similar to those seen with adolescent treatment. However, there was also evidence for drug-induced sensitization in adults that was not observed in adolescents. Thus, altered drug sensitivity in chronic Ecstasy users may depend not only on the frequency and pattern of use but also on the age of the user.

Authors+Show Affiliations

Neuroscience and Behavior Program, University of Massachusetts, Amherst, Massachusetts 01003, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20169574

Citation

Piper, Brian J., et al. "Repeated Intermittent Methylenedioxymethamphetamine Exposure Protects Against the Behavioral and Neurotoxic, but Not Hyperthermic, Effects of an MDMA Binge in Adult Rats." Synapse (New York, N.Y.), vol. 64, no. 6, 2010, pp. 421-31.
Piper BJ, Ali SF, Daniels LG, et al. Repeated intermittent methylenedioxymethamphetamine exposure protects against the behavioral and neurotoxic, but not hyperthermic, effects of an MDMA binge in adult rats. Synapse. 2010;64(6):421-31.
Piper, B. J., Ali, S. F., Daniels, L. G., & Meyer, J. S. (2010). Repeated intermittent methylenedioxymethamphetamine exposure protects against the behavioral and neurotoxic, but not hyperthermic, effects of an MDMA binge in adult rats. Synapse (New York, N.Y.), 64(6), pp. 421-31. doi:10.1002/syn.20744.
Piper BJ, et al. Repeated Intermittent Methylenedioxymethamphetamine Exposure Protects Against the Behavioral and Neurotoxic, but Not Hyperthermic, Effects of an MDMA Binge in Adult Rats. Synapse. 2010;64(6):421-31. PubMed PMID: 20169574.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Repeated intermittent methylenedioxymethamphetamine exposure protects against the behavioral and neurotoxic, but not hyperthermic, effects of an MDMA binge in adult rats. AU - Piper,Brian J, AU - Ali,Syed F, AU - Daniels,Lauren G, AU - Meyer,Jerrold S, PY - 2010/2/20/entrez PY - 2010/2/20/pubmed PY - 2010/7/20/medline SP - 421 EP - 31 JF - Synapse (New York, N.Y.) JO - Synapse VL - 64 IS - 6 N2 - We have recently shown that chronic intermittent exposure of adolescent rats to 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) completely blocks the reduction in serotonin transporter (SERT) binding and the hypoactivity seen following a subsequent MDMA binge treatment. The present study determined whether a similar neuroprotective effect also occurs in rats given the same intermittent MDMA exposure in adulthood. Adult male Sprague-Dawley rats were given either MDMA (10 mg/kg x 2) or saline, every fifth day, from postnatal day (PD) 60 to PD 85. The MDMA-induced latency until seminal plug production was reduced over the course of intermittent treatments. After a 1-week wash-out period, animals received either a low- or high-dose MDMA binge (2.5 or 5.0 mg/kg x 4). Core body temperature was measured during and after the binge to determine the effects of MDMA pretreatment on MDMA-induced hyperthermia. Spontaneous motor activity was determined the next day, and cortical and hippocampal samples were collected at 1 week postbinge to measure serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations as well as [3H]citalopram binding to SERT. Hyperthermia occurred more rapidly and seminal discharge was more common in the MDMA-pretreated group compared to the MDMA-naïve group in animals given the low-dose binge. MDMA preexposure protected animals from the reductions in cortical 5-HT levels and SERT binding produced by the high-dose binge and blocked the postbinge hypoactivity. These findings indicate that chronic, intermittent MDMA exposure in adulthood induces neuroprotective effects similar to those seen with adolescent treatment. However, there was also evidence for drug-induced sensitization in adults that was not observed in adolescents. Thus, altered drug sensitivity in chronic Ecstasy users may depend not only on the frequency and pattern of use but also on the age of the user. SN - 1098-2396 UR - https://www.unboundmedicine.com/medline/citation/20169574/Repeated_intermittent_methylenedioxymethamphetamine_exposure_protects_against_the_behavioral_and_neurotoxic_but_not_hyperthermic_effects_of_an_MDMA_binge_in_adult_rats_ L2 - https://doi.org/10.1002/syn.20744 DB - PRIME DP - Unbound Medicine ER -