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Effect of repeated ('binge') dosing of MDMA to rats housed at normal and high temperature on neurotoxic damage to cerebral 5-HT and dopamine neurones.
J Psychopharmacol 2004; 18(3):412-6JP

Abstract

The technique of 'binge' dosing (several doses in one session) by recreational users of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) requires evaluation in terms of its consequences on the acute hyperthermic response and long-term neurotoxicity. We examined the neurotoxic effects of this dosing schedule on 5-HT and dopamine neurones in the rat brain. When repeated (three) doses of MDMA (2, 4 and 6 mg/kg i.p.) were given 3 h apart to rats housed at 19 degrees C, a dose-dependent acute hyperthermia and long-term loss of 5-HT was observed in several brain regions (hippocampus, cortex and striatum), with an approximate 50% loss following 3 x 4 mg/kg and 65% decrease following 3 x 6 mg/kg. No decrease in striatal dopamine content was detected. When MDMA (4 mg/kg i.p.) was given repeatedly to rats housed at 30 degrees C, a larger acute hyperthermic response than that observed in rats treated at 19 degrees C environment was seen (maximum response 2.6 +/- 0.1 degrees C versus 1.3 +/- 0.2 degrees C). A long-term cerebral 5-HT loss of approximately 65% was also detected in both the cortex and hippocampus, but no loss in striatal dopamine content occurred. These data emphasize the increased acute hyperthermic response and neurotoxicity which occurs when MDMA is administered in a hot room environment compared to normal room temperature conditions, and support the view that MDMA is a selective 5-HT neurotoxin, even when a binge dosing schedule is employed and the rats are present in a hot environment.

Authors+Show Affiliations

Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15358986

Citation

Sanchez, Veronica, et al. "Effect of Repeated ('binge') Dosing of MDMA to Rats Housed at Normal and High Temperature On Neurotoxic Damage to Cerebral 5-HT and Dopamine Neurones." Journal of Psychopharmacology (Oxford, England), vol. 18, no. 3, 2004, pp. 412-6.
Sanchez V, O'shea E, Saadat KS, et al. Effect of repeated ('binge') dosing of MDMA to rats housed at normal and high temperature on neurotoxic damage to cerebral 5-HT and dopamine neurones. J Psychopharmacol (Oxford). 2004;18(3):412-6.
Sanchez, V., O'shea, E., Saadat, K. S., Elliott, J. M., Colado, M. I., & Green, A. R. (2004). Effect of repeated ('binge') dosing of MDMA to rats housed at normal and high temperature on neurotoxic damage to cerebral 5-HT and dopamine neurones. Journal of Psychopharmacology (Oxford, England), 18(3), pp. 412-6.
Sanchez V, et al. Effect of Repeated ('binge') Dosing of MDMA to Rats Housed at Normal and High Temperature On Neurotoxic Damage to Cerebral 5-HT and Dopamine Neurones. J Psychopharmacol (Oxford). 2004;18(3):412-6. PubMed PMID: 15358986.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of repeated ('binge') dosing of MDMA to rats housed at normal and high temperature on neurotoxic damage to cerebral 5-HT and dopamine neurones. AU - Sanchez,Veronica, AU - O'shea,Esther, AU - Saadat,Kathryn S, AU - Elliott,J Martin, AU - Colado,M Isabel, AU - Green,A Richard, PY - 2004/9/11/pubmed PY - 2005/3/18/medline PY - 2004/9/11/entrez SP - 412 EP - 6 JF - Journal of psychopharmacology (Oxford, England) JO - J. Psychopharmacol. (Oxford) VL - 18 IS - 3 N2 - The technique of 'binge' dosing (several doses in one session) by recreational users of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) requires evaluation in terms of its consequences on the acute hyperthermic response and long-term neurotoxicity. We examined the neurotoxic effects of this dosing schedule on 5-HT and dopamine neurones in the rat brain. When repeated (three) doses of MDMA (2, 4 and 6 mg/kg i.p.) were given 3 h apart to rats housed at 19 degrees C, a dose-dependent acute hyperthermia and long-term loss of 5-HT was observed in several brain regions (hippocampus, cortex and striatum), with an approximate 50% loss following 3 x 4 mg/kg and 65% decrease following 3 x 6 mg/kg. No decrease in striatal dopamine content was detected. When MDMA (4 mg/kg i.p.) was given repeatedly to rats housed at 30 degrees C, a larger acute hyperthermic response than that observed in rats treated at 19 degrees C environment was seen (maximum response 2.6 +/- 0.1 degrees C versus 1.3 +/- 0.2 degrees C). A long-term cerebral 5-HT loss of approximately 65% was also detected in both the cortex and hippocampus, but no loss in striatal dopamine content occurred. These data emphasize the increased acute hyperthermic response and neurotoxicity which occurs when MDMA is administered in a hot room environment compared to normal room temperature conditions, and support the view that MDMA is a selective 5-HT neurotoxin, even when a binge dosing schedule is employed and the rats are present in a hot environment. SN - 0269-8811 UR - https://www.unboundmedicine.com/medline/citation/15358986/Effect_of_repeated__'binge'__dosing_of_MDMA_to_rats_housed_at_normal_and_high_temperature_on_neurotoxic_damage_to_cerebral_5_HT_and_dopamine_neurones_ L2 - http://journals.sagepub.com/doi/full/10.1177/026988110401800312?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -