3,4-Methylenedioxymethamphetamine- and 8-hydroxy-2-di-n-propylamino- tetralin-induced hypothermia: Role and location of 5-hydroxytryptamine 1A receptors

Daniel E. Rusyniak, Maria V. Zaretskaia, Dmitry V. Zaretsky, Joseph A. DiMicco

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The popular drug of abuse 3,4-methylenedioxymethamphetamine (MDMA) has complex interactions with thermoregulatory systems, resulting in either hyperthermia or hypothermia. MDMA induces hypothermia when given to animals housed at a low ambient temperature. In this study we report that MDMA (7.5 mg/kg i.p.) given at normal ambient temperatures of 24 to 25°C caused, in conscious freely moving rats, hypothermia (mean decrease from baseline of 1.1 ± 0.06°C at 40 min). Pretreating animals with a 0.5 mg/kg i.p. dose of the 5-hydroxytryptamine 1A (5-HT1A) antagonist N-[2-[4-(2-methoxyphenyl)-1- piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY 100635) not only prevented MDMA-induced hypothermia, but resulted in the development of hyperthermia (mean temperature increase from baseline of 0.74 ± 0.2°C at 120 min). After treatment with WAY 100635, MDMA also elicited an enhanced tachycardia (mean increases in heart rate from baseline of 110 ± 16 beats/min at 90 min). To identify the location of 5-HT1A receptors responsible for hypothermia induced by MDMA, we first investigated the role of 5-HT1A receptors in the rostral raphe pallidus (rRP) in decreases in temperature evoked by the known 5-HT1A agonist 8-hydroxy-2-di-n- propylaminotetralin (DPAT). Microinjections of 0.5 nmol of WAY 100635 into the rRP significantly attenuated DPAT (0.2 mg/kg i.p.)-elicited hypothermia. In parallel experiments, we found that microinjections of WAY 100635 into the rRP, while significantly augmenting MDMA-mediated tachycardia, did not alter body temperature. These results demonstrate that although hypothermia mediated by both MDMA and DPAT shares a common dependence on the activation of 5-HT 1A receptors, the location of these receptors is different for each drug.

Original languageEnglish (US)
Pages (from-to)477-487
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume323
Issue number2
DOIs
StatePublished - Nov 2007

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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