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- Capela, J P (författare)
Ecstasy-induced cell death in cortical neuronal cultures is serotonin 2A-receptor-dependent and potentiated under hyperthermia
- Artikel/kapitelEngelska2006
Förlag, utgivningsår, omfång ...
- Elsevier BV,2006
Nummerbeteckningar
- LIBRIS-ID:oai:lup.lub.lu.se:41df206d-ef51-4e43-857b-5d032f413b5a
- https://lup.lub.lu.se/record/1136475URI
- https://doi.org/10.1016/j.neuroscience.2006.01.007DOI
Kompletterande språkuppgifter
- Språk:engelska
- Sammanfattning på:engelska
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- SwePubSwePub
Klassifikation
Anmärkningar
- Studies on 3,4-methylenedioxymethamphetamine ("ecstasy")-induced neurotoxicity mainly focus on damage of serotonergic terminals. Less attention has been given to neuronal cell death produced by 3,4-methylenedioxymethamphetamine and other amphetamines in areas including the cortex, striatum and thalamus. In the present study we investigated 3,4-methylenedioxymethamphetamine-induced neurotoxicity in neuronal serum free cultures from rat cortex. Since 3,4-methylenedioxymethamphetamine intake induces hyperthermia in both animals and humans, the experiments were performed under normal (36.5 degrees C) and hyperthermic conditions (40 degrees C). Our findings showed a dose-, time- and temperature-dependent apoptotic cell death induced by 3,4-methylenedioxymethamphetamine in cortical neurons. 3,4-Methylenedioxymethamphetamine-induced damage was potentiated under hyperthermia. The neurotoxicity was reduced by the serotonin 2A-receptor antagonists, ketanserin and (2R,4R)-5-[2-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]ethyl]-1-methyl-3-pyrrol idinol hydrochloride, in both normothermic and hyperthermic conditions. (+/-)-2,5-Dimethoxy-4-iodoamphetamine hydrochloride, a model agonist for the serotonin 2A-receptor, also induced a dose- and time-dependent apoptotic cell death. Again, protection was provided by ketanserin and (2R,4R)-5-[2-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]ethyl]-1-methyl-3-pyrrol idinol hydrochloride against (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride-induced neurotoxicity, thereby indicating that the 3,4-methylenedioxymethamphetamine stimulation of the serotonin 2A-receptor leads to neurotoxicity. This study provides for the first time evidence that direct 3,4-methylenedioxymethamphetamine serotonin 2A-receptor stimulation leads to neuronal cortical death. alpha-Phenyl-N-tert-butyl nitrone a free radical scavenger and the nitric oxide synthase inhibitor Nomega-nitro-L-arginine as well as the NMDA-receptor antagonist MK-801 provided protection under normothermia and hyperthermia, thereby suggesting the participation of free radicals in 3,4-methylenedioxymethamphetamine-induced cell death. Since 3,4-methylenedioxymethamphetamine serotonin 2A-receptor agonistic properties lead to neuronal death, clinically available atypical antipsychotic drugs with serotonin 2A-antagonistic properties could be a valuable therapeutic tool against 3,4-methylenedioxymethamphetamine-induced neurodegeneration.
Ämnesord och genrebeteckningar
- MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
- MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
- MDMA
- primary cortical neuronal serum free culture
- hyperthermia
- apoptosis
- neurotoxicity
- 5-HT2A-receptor
Biuppslag (personer, institutioner, konferenser, titlar ...)
- Ruscher, KarstenLund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-ktr (författare)
- Lautenschlager, M (författare)
- Freyer, D (författare)
- Dirnagl, U (författare)
- Gaio, A R (författare)
- Bastos, M L (författare)
- Meisel, A (författare)
- Carvalho, F (författare)
- NeurokirurgiSektion IV (creator_code:org_t)
Sammanhörande titlar
- Ingår i:Neuroscience: Elsevier BV139:3, s. 1069-10811873-75440306-4522
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