Aged rats are more vulnerable than adolescents to “ecstasy”-induced toxicity

Aged rats are more vulnerable than adolescents to “ecstasy”-induced toxicity 3,4-Methylenedioxymethamphetamine (MDMA or “ecstasy”) is a widespread drug of abuse with known neurotoxic properties. The present study aimed to evaluate the differential toxic effects of MDMA in adolescent and aged Wistar rats, using doses pharmacologically comparable to humans. Adolescent (post-natal day 40) (3 × 5 mg/kg, 2 h apart) and aged (mean 20 months old) (2 × 5 mg/kg, 2 h apart) rats received MDMA intraperitoneally. Animals were killed 7 days later, and the frontal cortex, hippocampus, striatum and cerebellum brain areas were dissected, and heart, liver and kidneys were collected. MDMA caused hyperthermia in both treated groups, but aged rats had a more dramatic temperature elevation. MDMA promoted serotonergic neurotoxicity only in the hippocampus of aged, but not in the adolescents’ brain, and did not change the levels of dopamine or serotonin metabolite in the striatum of both groups. Differential responses according to age were also seen regarding brain p-Tau levels, a hallmark of a degenerative brain, since only aged animals had significant increases. MDMA evoked brain oxidative stress in the hippocampus and striatum of aged, and in the hippocampus, frontal cortex, and striatum brain areas of adolescents according to protein carbonylation, but only decreased GSH levels in the hippocampus of aged animals. The brain maturational stage seems crucial for MDMA-evoked serotonergic neurotoxicity. Aged animals were more susceptible to MDMA-induced tissue damage in the heart and kidneys, and both ages had an increase in liver fibrotic tissue content. In conclusion, age is a determinant factor for the toxic events promoted by “ecstasy”. This work demonstrated special susceptibility of aged hippocampus to MDMA neurotoxicity, as well as impressive damage to the heart and kidney tissue following “ecstasy”. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Toxicology Springer Journals

Aged rats are more vulnerable than adolescents to “ecstasy”-induced toxicity

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Publisher
Springer Berlin Heidelberg
Copyright
Copyright © 2018 by Springer-Verlag GmbH Germany, part of Springer Nature
Subject
Biomedicine; Pharmacology/Toxicology; Occupational Medicine/Industrial Medicine; Environmental Health; Biomedicine, general
ISSN
0340-5761
eISSN
1432-0738
D.O.I.
10.1007/s00204-018-2226-8
Publisher site
See Article on Publisher Site

Abstract

3,4-Methylenedioxymethamphetamine (MDMA or “ecstasy”) is a widespread drug of abuse with known neurotoxic properties. The present study aimed to evaluate the differential toxic effects of MDMA in adolescent and aged Wistar rats, using doses pharmacologically comparable to humans. Adolescent (post-natal day 40) (3 × 5 mg/kg, 2 h apart) and aged (mean 20 months old) (2 × 5 mg/kg, 2 h apart) rats received MDMA intraperitoneally. Animals were killed 7 days later, and the frontal cortex, hippocampus, striatum and cerebellum brain areas were dissected, and heart, liver and kidneys were collected. MDMA caused hyperthermia in both treated groups, but aged rats had a more dramatic temperature elevation. MDMA promoted serotonergic neurotoxicity only in the hippocampus of aged, but not in the adolescents’ brain, and did not change the levels of dopamine or serotonin metabolite in the striatum of both groups. Differential responses according to age were also seen regarding brain p-Tau levels, a hallmark of a degenerative brain, since only aged animals had significant increases. MDMA evoked brain oxidative stress in the hippocampus and striatum of aged, and in the hippocampus, frontal cortex, and striatum brain areas of adolescents according to protein carbonylation, but only decreased GSH levels in the hippocampus of aged animals. The brain maturational stage seems crucial for MDMA-evoked serotonergic neurotoxicity. Aged animals were more susceptible to MDMA-induced tissue damage in the heart and kidneys, and both ages had an increase in liver fibrotic tissue content. In conclusion, age is a determinant factor for the toxic events promoted by “ecstasy”. This work demonstrated special susceptibility of aged hippocampus to MDMA neurotoxicity, as well as impressive damage to the heart and kidney tissue following “ecstasy”.

Journal

Archives of Toxicology – Springer Journals

Published: Jun 4, 2018

References

  • Recovery and aging of serotonergic fibers after single and intermittent MDMA treatment in dark agouti rat
    Ádori, C; Andó, RD; Szekeres, M; Gutknecht, L; Kovács, GG; Hunyady, L; Lesch, K-P; Bagdy, G
  • Monoamine oxidase-B mediates ecstasy-induced neurotoxic effects to adolescent rat brain mitochondria
    Alves, E; Summavielle, T; Alves, CJ; Gomes-da-Silva, J; Barata, JC; Fernandes, E; Bastos, ML; Tavares, MA; Carvalho, F
  • Acetyl-l-carnitine provides effective in vivo neuroprotection over 3,4-methylenedioximethamphetamine-induced mitochondrial neurotoxicity in the adolescent rat brain
    Alves, E; Binienda, Z; Carvalho, F; Alves, CJ; Fernandes, E; Bastos, ML; Tavares, MA; Summavielle, T
  • Ecstasy: a common cause of severe acute hepatotoxicity
    Andreu, V; Mas, A; Bruguera, M; Salmeron, JM; Moreno, V; Nogue, S; Rodes, J
  • Multiple MDMA (Ecstasy) overdoses at a rave event: a case series
    Armenian, P; Mamantov, TM; Tsutaoka, BT; Gerona, RR; Silman, EF; Wu, AH; Olson, KR
  • Changes in cardiovascular responsiveness and cardiotoxicity elicited during binge administration of Ecstasy
    Badon, LA; Hicks, A; Lord, K; Ogden, BA; Meleg-Smith, S; Varner, KJ
  • Detection of elevated caspase activation and early apoptosis in liver diseases
    Bantel, H; Ruck, P; Gregor, M; Schulze-Osthoff, K
  • Pro-oxidant effects of Ecstasy and its metabolites in mouse brain synaptosomes
    Barbosa, DJ; Capela, JP; Oliveira, JM; Silva, R; Ferreira, LM; Siopa, F; Branco, PS; Fernandes, E; Duarte, JA; Bastos, ML; Carvalho, F
  • The mixture of “ecstasy” and its metabolites is toxic to human SH-SY5Y differentiated cells at in vivo relevant concentrations
    Barbosa, DJ; Capela, JP; Silva, R; Vilas-Boas, V; Ferreira, LM; Branco, PS; Fernandes, E; Bastos, ML; Carvalho, F
  • The mixture of “ecstasy” and its metabolites impairs mitochondrial fusion/fission equilibrium and trafficking in hippocampal neurons, at in vivo relevant concentrations
    Barbosa, DJ; Serrat, R; Mirra, S; Quevedo, M; Barreda, EG; Avila, J; Ferreira, LM; Branco, PS; Fernandes, E; Bastos, ML; Capela, JP; Soriano, E; Carvalho, F
  • MDMA impairs mitochondrial neuronal trafficking in a Tau- and Mitofusin2/Drp1-dependent manner
    Barbosa, DJ; Serrat, R; Mirra, S; Quevedo, M; Gómez de Barreda, E; Ávila, J; Fernandes, E; Bastos, ML; Capela, JP; Carvalho, F; Soriano, E
  • Mitochondria: key players in the neurotoxic effects of amphetamines
    Barbosa, DJ; Capela, JP; Feio-Azevedo, R; Teixeira-Gomes, A; Bastos, ML; Carvalho, F
  • Haye’s principles and methods of toxicology
    Beck, BD; Seeley, M; Calabrese, EJ
  • Age-dependent sensitivity of rats to the long-term effects of the serotonergic neurotoxicant (+/)-3,4-methylenedioxymethamphetamine (MDMA) correlates with the magnitude of the MDMA-induced thermal response
    Broening, HW; Bowyer, JF; Slikker, W
  • Enhanced tau phosphorylation in the Hippocampus of Mice Treated with 3,4-methylenedioxymethamphetamine (“Ecstasy”)
    Busceti, CL; Biagioni, F; Riozzi, B; Battaglia, G; Storto, M; Cinque, C; Molinaro, G; Gradini, R; Caricasole, A; Canudas, AM; Bruno, V; Nicoletti, F; Fornai, F
  • Neurotoxicity of Ecstasy metabolites in rat cortical neurons, and influence of hyperthermia
    Capela, JP; Meisel, A; Abreu, AR; Branco, PS; Ferreira, LM; Lobo, AM; Remiao, F; Bastos, ML; Carvalho, F
  • Neurotoxicity mechanisms of thioether ecstasy metabolites
    Capela, JP; Macedo, C; Branco, PS; Ferreira, LM; Lobo, AM; Fernandes, E; Remiao, F; Bastos, ML; Dirnagl, U; Meisel, A; Carvalho, F
  • Molecular and cellular mechanisms of ecstasy-induced neurotoxicity: an overview
    Capela, JP; Carmo, H; Remiao, F; Bastos, ML; Meisel, A; Carvalho, F
  • Toxicity of amphetamines: an update
    Carvalho, M; Carmo, H; Costa, VM; Capela, JP; Pontes, H; Remião, F; Carvalho, F; Bastos, ML
  • Body temperature effect on methylenedioxymethamphetamine-induced acute decrease in tryptophan hydroxylase activity
    Che, S; Johnson, M; Hanson, GR; Gibb, JW
  • A study of the neurotoxic effect of MDMA (‘ecstasy’) on 5-HT neurones in the brains of mothers and neonates following administration of the drug during pregnancy
    Colado, MI; O’Shea, E; Granados, R; Misra, A; Murray, TK; Green, AR
  • Oxidation process of adrenaline in freshly isolated rat cardiomyocytes: formation of adrenochrome, quinoproteins, and GSH adduct
    Costa, VM; Silva, R; Ferreira, LM; Branco, PS; Carvalho, F; Bastos, ML; Carvalho, RA; Carvalho, M; Remiao, F
  • Contribution of catecholamine reactive intermediates and oxidative stress to the pathologic features of heart diseases
    Costa, VM; Carvalho, F; Bastos, ML; Carvalho, RA; Carvalho, M; Remiao, F
  • Reduced cortical gray matter density in human MDMA (Ecstasy) users: a voxel-based morphometry study
    Cowan, RL; Lyoo, IK; Sung, SM; Ahn, KH; Kim, MJ; Hwang, J; Haga, E; Vimal, RLP; Lukas, SE; Renshaw, PF
  • 3,4-methylenedioxymethamphetamine induces gene expression changes in rats related to serotonergic and dopaminergic systems, but not to neurotoxicity
    Cuyas, E; Robledo, P; Pizarro, N; Farre, M; Puerta, E; Aguirre, N; Torre, R
  • Catecholamine Metabolism in Experimental Hypertension in the Rat
    Champlain, J; Krakoff, LR; Axelrod, J
  • The age factor for mitoxantrone’s cardiotoxicity: Multiple doses render the adult mouse heart more susceptible to injury
    Dores-Sousa, JL; Duarte, JA; Seabra, V; Bastos, ML; Carvalho, F; Costa, VM
  • European Drug Report 2017: Trends and developments
  • Chronic MDMA induces neurochemical changes in the hippocampus of adolescent and young adult rats: down-regulation of apoptotic markers
    Garcia-Cabrerizo, R; Garcia-Fuster, MJ
  • The relationship between core body temperature and 3,4-methylenedioxymethamphetamine metabolism in rats: implications for neurotoxicity
    Goni-Allo, B; B, OM; Segura, M; Puerta, E; Lasheras, B; Torre, R; Aguirre, N
  • On the role of tyrosine and peripheral metabolism in 3,4-methylenedioxymethamphetamine-induced serotonin neurotoxicity in rats
    Goni-Allo, B; Puerta, E; Mathuna, BO; Hervias, I; Lasheras, B; Torre, R; Aguirre, N
  • Multiple toxicity from 3,4-methylenedioxymethamphetamine (“ecstasy”)
    Greene, SL; Dargan, PI; O’Connor, N; Jones, AL; Kerins, M
  • Acute toxic effects of ‘Ecstasy’ (MDMA) and related compounds: overview of pathophysiology and clinical management
    Hall, AP; Henry, JA
  • Toxicity and deaths from 3,4-methylenedioxymethamphetamine (“ecstasy”)
    Henry, JA; Jeffreys, KJ; Dawling, S
  • Mechanisms of tau-induced neurodegeneration
    Iqbal, K; Liu, F; Gong, C-X; Alonso, AdC; Grundke-Iqbal, I
  • Nephroprotective effects of Feijoa sellowiana leaves extract on renal injury induced by acute dose of ecstasy (MDMA) in mice
    Karami, M; Karimian Nokabadi, F; Ebrahimzadeh, MA; Naghshvar, F
  • Functional consequences of perinatal exposure to 3,4-methylenedioxymethamphetamine in rat brain
    Kelly, PA; Ritchie, IM; Quate, L; McBean, DE; Olverman, HJ
  • Repeated intermittent MDMA binges reduce DAT density in mice and SERT density in rats in reward regions of the adolescent brain
    Kindlundh-Hogberg, AM; Schioth, HB; Svenningsson, P
  • The effects of ecstasy (MDMA) on brain serotonin transporters are dependent on age-of-first exposure in recreational users and animals
    Klomp, A; Hollander, B; Bruin, K; Booij, J; Reneman, L
  • Increased anxiety-related behavior in male and female adult rats following early and late adolescent exposure to 3,4-methylenedioxymethamphetamine (MDMA)
    Kolyaduke, OV; Hughes, RN
  • Influence of aging on tissue-specific noradrenergic activity at rest and during nonexertional heating in rats
    Kregel, KC
  • Methylphenidate clinically oral doses improved brain and heart glutathione redox status and evoked renal and cardiac tissue injury in rats
    Loureiro-Vieira, S; Costa, VM; Duarte, JA; Duarte-Araújo, M; Gonçalves-Monteiro, S; Maria Lourdes, B; Carvalho, F; Capela, JP
  • Small changes in ambient temperature cause large changes in 3,4-methylenedioxymethamphetamine (MDMA)-induced serotonin neurotoxicity and core body temperature in the rat
    Malberg, JE; Seiden, LS
  • Co-administration of MDMA with drugs that protect against MDMA neurotoxicity produces different effects on body temperature in the rat
    Malberg, JE; Sabol, KE; Seiden, LS
  • The role of the sympathetic nervous system and uncoupling proteins in the thermogenesis induced by 3,4-methylenedioxymethamphetamine
    Mills, EM; Rusyniak, DE; Sprague, JE
  • Binge ethanol and MDMA combination exacerbates toxic cardiac effects by inducing cellular stress
    Navarro-Zaragoza, J; Ros-Simo, C; Milanes, MV; Valverde, O; Laorden, ML
  • Age-related decrease of serotonergic fibres and S-100[beta] immunoreactivity in the rat dentate gyrus
    Nishimura, A; Ueda, S; Takeuchi, Y; Sawada, T; Kawata, M
  • Buprenorphine modulates methamphetamine-induced dopamine dynamics in the rat caudate nucleus
    Pereira, FC; Gough, B; Macedo, TR; Ribeiro, CF; Ali, SF; Binienda, ZK
  • Age-dependent (+)MDMA-mediated neurotoxicity in mice
    Reveron, ME; Monks, TJ; Duvauchelle, CL
  • Ecstasy produces left ventricular dysfunction and oxidative stress in rats
    Shenouda, SK; Lord, KC; McIlwain, E; Lucchesi, PA; Varner, KJ
  • MDMA induces cardiac contractile dysfunction through autophagy upregulation and lysosome destabilization in rats
    Shintani-ishida, K; Saka, K; Yamaguchi, K; Hayashida, M; Nagai, H; Takemura, G; Yoshida, K
  • Cellular determinants of reduced adaptability of the aging brain: neurotransmitter utilization and cell signaling responses after MDMA lesions
    Slotkin, TA; Seidler, FJ; Ali, SF
  • Inflammasomes in liver diseases
    Szabo, G; Csak, T
  • The neurotoxicity of amphetamines during the adolescent period
    Teixeira-Gomes, A; Costa, VM; Feio-Azevedo, R; Bastos, ML; Carvalho, F; Capela, JP
  • “Ecstasy” toxicity to adolescent rats following an acute low binge dose
    Teixeira-Gomes, A; Costa, VM; Feio-Azevedo, R; Duarte, JA; Duarte-Araújo, M; Fernandes, E; Bastos, ML; Carvalho, F; Capela, JP
  • World Drug Report 2017
  • Aberrant morphology of serotonergic fibers in the forebrain of the aged rat
    Luijtelaar, MGPA; Steinbusch, HWM; Tonnaer, JADM
  • Morphological changes during acute experimental short-term hyperthermia
    Vlad, M; Ionescu, N; Ispas, AT; Giuvarasteanu, I; Ungureanu, E; Stoica, C
  • Tissue concentrations of 4-HNE in the black walnut extract model of laminitis: indication of oxidant stress in affected laminae
    Yin, C; Pettigrew, A; Loftus, JP; Black, SJ; Belknap, JK

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