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3,4-Methylenedioxymethamphetamine- and 8-hydroxy-2-di-n-propylamino-tetralin-induced hypothermia: role and location of 5-hydroxytryptamine 1A receptors.
J Pharmacol Exp Ther. 2007 Nov; 323(2):477-87.JP

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 degrees C caused, in conscious freely moving rats, hypothermia (mean decrease from baseline of 1.1 +/- 0.06 degrees C at 40 min). Pretreating animals with a 0.5 mg/kg i.p. dose of the 5-hydroxytryptamine 1A (5-HT(1A)) 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 degrees 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-HT(1A) receptors responsible for hypothermia induced by MDMA, we first investigated the role of 5-HT(1A) receptors in the rostral raphe pallidus (rRP) in decreases in temperature evoked by the known 5-HT(1A) agonist 8-hydroxy-2-di-n-propylamino-tetralin (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.

Authors+Show Affiliations

Departments of Emergency Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA. drusynia@iupui.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17702902

Citation

Rusyniak, Daniel E., et al. "3,4-Methylenedioxymethamphetamine- and 8-hydroxy-2-di-n-propylamino-tetralin-induced Hypothermia: Role and Location of 5-hydroxytryptamine 1A Receptors." The Journal of Pharmacology and Experimental Therapeutics, vol. 323, no. 2, 2007, pp. 477-87.
Rusyniak DE, Zaretskaia MV, Zaretsky DV, et al. 3,4-Methylenedioxymethamphetamine- and 8-hydroxy-2-di-n-propylamino-tetralin-induced hypothermia: role and location of 5-hydroxytryptamine 1A receptors. J Pharmacol Exp Ther. 2007;323(2):477-87.
Rusyniak, D. E., Zaretskaia, M. V., Zaretsky, D. V., & DiMicco, J. A. (2007). 3,4-Methylenedioxymethamphetamine- and 8-hydroxy-2-di-n-propylamino-tetralin-induced hypothermia: role and location of 5-hydroxytryptamine 1A receptors. The Journal of Pharmacology and Experimental Therapeutics, 323(2), 477-87.
Rusyniak DE, et al. 3,4-Methylenedioxymethamphetamine- and 8-hydroxy-2-di-n-propylamino-tetralin-induced Hypothermia: Role and Location of 5-hydroxytryptamine 1A Receptors. J Pharmacol Exp Ther. 2007;323(2):477-87. PubMed PMID: 17702902.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 3,4-Methylenedioxymethamphetamine- and 8-hydroxy-2-di-n-propylamino-tetralin-induced hypothermia: role and location of 5-hydroxytryptamine 1A receptors. AU - Rusyniak,Daniel E, AU - Zaretskaia,Maria V, AU - Zaretsky,Dmitry V, AU - DiMicco,Joseph A, Y1 - 2007/08/16/ PY - 2007/8/19/pubmed PY - 2007/12/7/medline PY - 2007/8/19/entrez SP - 477 EP - 87 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 323 IS - 2 N2 - 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 degrees C caused, in conscious freely moving rats, hypothermia (mean decrease from baseline of 1.1 +/- 0.06 degrees C at 40 min). Pretreating animals with a 0.5 mg/kg i.p. dose of the 5-hydroxytryptamine 1A (5-HT(1A)) 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 degrees 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-HT(1A) receptors responsible for hypothermia induced by MDMA, we first investigated the role of 5-HT(1A) receptors in the rostral raphe pallidus (rRP) in decreases in temperature evoked by the known 5-HT(1A) agonist 8-hydroxy-2-di-n-propylamino-tetralin (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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/17702902/34_Methylenedioxymethamphetamine__and_8_hydroxy_2_di_n_propylamino_tetralin_induced_hypothermia:_role_and_location_of_5_hydroxytryptamine_1A_receptors_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=17702902 DB - PRIME DP - Unbound Medicine ER -