CuZn-superoxide dismutase (CuZnSOD) transgenic mice show resistance to the lethal effects of methylenedioxyamphetamine (MDA) and of methylenedioxymethamphetamine (MDMA)

Cadet, Jean Lud; Ladenheim, Bruce; Baum, Ira; Carlson, Elaine; Epstein, Charles J.

doi:10.1016/0006-8993(94)91624-1

Cited by 89 publications

(41 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…13 Other possible mechanisms also include: (i) increased metabolism of DA released by MDMA; 13,22,38 and (ii) formation of DA metabolites such as 6-hydroxydopamine which is known to cause oxidative stress. 4,11 The possible role of reactive oxygen species in MDMA-induced toxicity is further supported by our previous observations that transgenic mice that have high levels of the antioxidant enzyme copper/zinc superoxide dismutase (Cu/ ZnSOD) in the brain were protected against the acute lethal effects of MDMA 7 and against the subacute and long-term toxic effects of the drug on brain DA systems. 9 Thus, we reasoned that, if MDMA was indeed causing oxidative stress in the brain, it might perturb the activities of various antioxidant enzymes (Cu/ ZnSOD, catalase, glutathione peroxidase) which participate in a concerted collaboration with each other in order to protect the brain against oxidative damage.…”

mentioning

confidence: 85%

“…In contrast, injections of MDMA to mice caused striatal dopamine (DA) depletion without significantly affecting serotonergic systems, when the animals were killed three to eight days 24 or two weeks later. 7,31 Moreover, large differences in sensitivity to the DA-depleting properties of MDMA have been reported among different strains of mice. 45 Although the cause of MDMA-induced neurotoxicity has not been fully determined, a number of possible scenarios have been put forward.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Overexpression of human copper/zinc superoxide dismutase in transgenic mice attenuates oxidative stress caused by methylenedioxymethamphetamine (Ecstasy)

et al. 1999

View full text Add to dashboard Cite

mentioning

confidence: 85%

mentioning

confidence: 99%

Overexpression of human copper/zinc superoxide dismutase in transgenic mice attenuates oxidative stress caused by methylenedioxymethamphetamine (Ecstasy)

et al. 1999

View full text Add to dashboard Cite

“…Despite the evidence for a role of free radicals in the damage using in vivo microdialysis techniques Camarero et al, 2002), a clear protective action of the nitrone radical trap PBN was not observed. However, this was primarily due to the investigators being unable to separate neuroprotection from a hypothermic action of PBN, and the involvement of free radicals in the longterm damage to dopamine neurons seen in mice does seem clear since studies using CuZn-superoxide dismutase-transgenic mice have demonstrated their resistance to MDMA-induced neurotoxicity (Cadet et al, 1994(Cadet et al, , 1995.…”

Section: Long-term Dopamine Depletionmentioning

confidence: 99%

The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)

Green

Mechan

Elliott

et al. 2003

Pharmacological Reviews

1,107

1,198

View full text Add to dashboard Cite

“…A large MDMA dose (80 mg/kg) was lethal in ninety percent of male mice versus less than one-third of females [18]. Similarly, male pubescent (PD 39) rats were shown to be much more sensitive to ecstasy in that MDMA doses that killed all males were non-fatal for most females.…”

Section: Sex-differencesmentioning

confidence: 99%

A developmental comparison of the neurobehavioral effects of ecstasy (MDMA)

Piper

2007

Neurotoxicology and Teratology

View full text Add to dashboard Cite

The entactogen ±3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a popular recreational drug among college, high school, and, occasionally, middle school students. Preclinical research examining the acute and long-term effects of MDMA has predominately been conducted in reproductively mature subjects but there has been increasing interest in adolescent and in utero exposure. This review examines the acute and long-term responses to MDMA during perinatal, adolescent, and adult periods. The ability of MDMA to alter core body temperature emerges gradually during ontogeny while a reduction in body weight is evident at all ages. Learning and workingmemory are also altered independent of the developmental stage of exposure. Current evidence suggests adults are more sensitive to the long-term serotonin depletions following MDMA but younger ages also exhibit substantial and rapid neuroplasticity. Sexually dimorphic MDMA responses have been identified for the acute hyperthermic and motoric effects of MDMA with pubescent males being especially susceptible. Several physiological, behavioral, and neurochemical MDMA issues requiring further study are also outlined. Keywords±3; 4-methylenedioxymethamphetamine; Adolescence; Anxiety; Depression; Learning; SerotoninThe phenylethylamine ±3,4-methylenedioxymethamphetamine (MDMA) is a popular recreational drug best known as ecstasy. MDMA has several other street names including Adam, baby slits, chocolate chips, clarity, doctor, essence, kleenex, and roll [77]. Although ecstasy has some similarities with both stimulants and hallucinogens, MDMA is an entactogen. Entactogen means "touching within" based on the drug's subjective effects [110]. MDMA also causes long term changes in several markers of the integrity of the serotonin (5-HT) neurotransmitter system [58]. There have been several excellent recent reviews on MDMA toxicology, pharmacokinetics, pharmacodynamics, and neurobehavioral consequences [30,37,113,157], but none have systematically addressed the intricate effects of MDMA during development.Ecstasy use is not restricted to limited subpopulations, that is fans of techno music and "raves" [173] or male homosexuals [73,81], as MDMA has expanded into the general population [124,148,170] and especially young people [52,78,170,172]. Over one hundred pregnant women in Toronto called a substance abuse helpline between 1998 and 2000 to inquire Corresponding Author: Brian J. Piper, Neuroscience and Behavior Program, University of Massachusetts, Amherst, MA 01003-7710, Tel: (413) 545-0996, bpiper@nsm.umass.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers...

show abstract

CuZn-superoxide dismutase (CuZnSOD) transgenic mice show resistance to the lethal effects of methylenedioxyamphetamine (MDA) and of methylenedioxymethamphetamine (MDMA)

Cited by 89 publications

References 10 publications

Overexpression of human copper/zinc superoxide dismutase in transgenic mice attenuates oxidative stress caused by methylenedioxymethamphetamine (Ecstasy)

Overexpression of human copper/zinc superoxide dismutase in transgenic mice attenuates oxidative stress caused by methylenedioxymethamphetamine (Ecstasy)

The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)

A developmental comparison of the neurobehavioral effects of ecstasy (MDMA)

Contact Info

Product

Resources

About