Altered prolactin response to M‐chlorophenylpiperazine in monkeys previously treated with 3,4‐methylenedioxymethamphetamine (MDMA) or fenfluramine

Hatzidimitriou, George; Tsai, Elizabeth H.; McCann, Una D.; Ricaurte, George A.

doi:10.1002/syn.10055

Cited by 14 publications

(11 citation statements)

References 35 publications

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“…Indeed, this "blunting" of the prolactin response has been suggested to be a marker of the integrity of serotonin systems (Hatzidimitriou et al, 2002;Baumann et al, 2008). However, previous studies have also shown that basal levels of prolactin are unaltered by exposure to MDMA (Hatzidimitriou et al, 2002).…”

Section: Effects Of S(ϩ)-mdma (F) Sr(ϯ)-mdma (‚) and R(ϫ)-mdmamentioning

confidence: 94%

“…As such, if the stereoisomers of MDMA have qualitatively different behavioral or interoceptive effects they should concomitantly exhibit qualitatively different endocrine and neurochemical effects. In support of this contention, it has been shown that S(ϩ)-MDMA increases extracellular dopamine turnover in the striatum (Hatzidimitriou et al, 2002;Acquas et al, 2007) and significantly occupies the dopamine transporter (Fantegrossi, 2008), whereas R(Ϫ)-MDMA does not. However, to date, the effects of the stereoisomers of MDMA on release of dopamine and serotonin and secretion of prolactin have not been comprehensively studied.…”

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confidence: 89%

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Endocrine and Neurochemical Effects of 3,4-Methylenedioxymethamphetamine and Its Stereoisomers in Rhesus Monkeys

Murnane¹,

Fantegrossi²,

Godfrey³

et al. 2010

J Pharmacol Exp Ther

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3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative that elicits complex biological effects in humans. One plausible mechanism for this phenomenon is that racemic MDMA is composed of two stereoisomers that exhibit qualitatively different pharmacological effects. In support of this, studies have shown that R(Ϫ)-MDMA tends to have hallucinogen-like effects, whereas S(ϩ)-MDMA tends to have psychomotor stimulant-like effects. However, relatively little is known about whether these stereoisomers engender different endocrine and neurochemical effects. In the present study, the endocrine and neurochemical effects of each stereoisomer and the racemate were assessed in four rhesus monkeys after intravenous delivery at doses (1-3 mg/kg) that approximated voluntary self-administration by rhesus monkeys and human recreational users. Specifically, fluorescence-based enzymelinked immunosorbent assay was used to assess plasma prolactin concentrations, and in vivo microdialysis was used to assess extracellular dopamine and serotonin concentrations in the dorsal striatum. R(Ϫ)-MDMA, but not S(ϩ)-MDMA, significantly increased plasma prolactin levels and the effects of S,R(Ϯ)-MDMA were intermediate to each of its component stereoisomers. Although S(ϩ)-MDMA did not alter prolactin levels, it did significantly increase extracellular serotonin concentrations. In addition, S(ϩ)-MDMA, but not R(Ϫ)-MDMA, significantly increased dopamine concentrations. Furthermore, as in the prolactin experiment, the effects of the racemate were intermediate to each of the stereoisomers. These studies demonstrate the stereoisomers of MDMA engender qualitatively different endocrine and neurochemical effects, strengthening the inference that differences in these stereoisomers might be the mechanism producing the complex biological effects of the racemic mixture of MDMA in humans.Racemic 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is a substituted phenethylamine with significant abuse liability. Although MDMA was placed into Schedule 1 of the Controlled Substances Act, its behavioral effects do not clearly fit into traditional delineations of drugs of abuse. Specifically, the racemic mixture of MDMA has both stimulant and hallucinogen-like effects (Shulgin, 1986;Harris et al., 2002). Moreover, Nichols (1986) postulated that MDMA represented a new class of compounds categorized as "entactogens." In support for this new categorization, Johanson et al. (2006) reported that in a three-choice discrimination procedure approximately half of the human subjects reported that MDMA was similar to the substrate-based dopamine releaser S(ϩ)-amphetamine, whereas the other half reported that it was similar to the serotonin releaser meta-chlorophenylpiperazine (mCPP).Previous studies have suggested that these complex effects are mediated by qualitative differences (i.e., apparent efficacy differences) between MDMA's stereoisomers. For example, one of the earliest studies contrasted the subjective effects of these stereoisomers in humans (A...

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Section: Effects Of S(ϩ)-mdma (F) Sr(ϯ)-mdma (‚) and R(ϫ)-mdmamentioning

confidence: 94%

mentioning

confidence: 89%

Endocrine and Neurochemical Effects of 3,4-Methylenedioxymethamphetamine and Its Stereoisomers in Rhesus Monkeys

Murnane¹,

Fantegrossi²,

Godfrey³

et al. 2010

J Pharmacol Exp Ther

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“…A series of studies on primates over the last 15 years all reported significant damage to 5-HT nerve terminals following MDMA administration (Ricaurte et al 1988a(Ricaurte et al , 1988b(Ricaurte et al , 1988cSlikker et al 1988Slikker et al , 1989Insel et al 1989;Kleven et al 1989;Wilson et al 1989;Ricaurte and McCann 1992;Fischer et al 1995;Scheffel et al 1998;Hatzidimitriou et al 1999Hatzidimitriou et al , 2002, but none reported evidence of damage to dopaminergic terminals when this had also been studied (Ricaurte et al 1988a;Slikker et al 1988;Insel et al 1989;Ricaurte and McCann 1992;Hatzidimitriou et al 1999). Even high doses of MDMA producing almost total loss (90%) of 5-HT in the caudate nucleus of squirrel monkeys left dopamine and noradrenaline levels unaffected (Ricaurte et al 1988a).…”

Section: Primatesmentioning

confidence: 94%

Acute and long-term effects of MDMA on cerebral dopamine biochemistry and function

2004

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MDMA appears to produce a major release of dopamine from its nerve endings in all species investigated. This release plays a significant role in the expression of many of the behaviours that occur, including behavioural changes, alterations of the mental state in humans and the potentially life-threatening hyperthermia that can occur. While MDMA appears to be a selective 5-HT neurotoxin in most species examined (rats, guinea pigs and primates), it is a selective dopamine neurotoxin in mice. Selectivity may be a consequence of what neurotoxic metabolites are produced (which may depend on dosing schedules), their selectivity for monoamine nerve endings, or the endogenous free radical trapping ability of specific nerve endings, or both. We suggest more focus be made on the actions of MDMA on dopamine neurochemistry and function to provide a better understanding of the acute and long-term consequences of using this popular recreational drug.

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“…The affinity to postsynaptic 5-HT 2 -receptors is likely to mediate the mild hallucinogenic effects of RSAs (7,44). Furthermore, several neuroendocrine effects observed in animal (41,62) and human studies (40,50,51,55) are thought to contribute to the central and peripheral effects of these drugs.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

The Neuropsychopharmacology and Toxicology of 3,4‐methylenedioxy‐N‐ethyl‐amphetamine (MDEA)

Freudenmann

Spitzer

2004

CNS Drug Reviews

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This paper reviews the pharmacology and toxicology of 3,4-methylenedioxy-N-ethylamphetamine (MDEA, "eve"). MDEA is a ring-substituted amphetamine (RSA) like MDMA, its well known N-methyl analog. Both have become very popular substances of abuse in the techno-and house-music scene. They can evoke psychomotor stimulation, mild alterations of perception, sensations of closeness and a positive emotional state as well as sympathomimetic physical effects. At present, the name "ecstasy" is no longer used only for MDMA, but for the whole group of RSAs (MDA, MDMA, MDEA and MBDB) as they are chemically and pharmacologically nearly identical; moreover, many ecstasy pills contain mixtures of the RSAs. Hence, for a selective review on MDEA, it is crucial to strictly differentiate between: 1) street and chemical names, and 2) studies with or without chemically defined substances. In order to present MDEA-specific information, the pharmacodynamics and kinetics are described on the basis of MDEA challenge studies in animals and humans. In the toxicology section, we present a collection of case reports on fatalities where MDEA was toxicologically confirmed. On the question of serotonergic neurotoxicity and possible long-term consequences, however, MDEA-specific information is available from animal studies only. The neurotoxic potential of MDEA in humans is difficult to estimate, as ecstasy users do not consume pure substances. For future research, challenge studies in animals using dosing regimens adapted to human consumption patterns are needed. Such challenge studies should directly compare individual RSAs. They will represent the most viable and fruitful approach to the resolution of the highly controversial issues of serotonergic neurotoxicity and its functional consequences.

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Altered prolactin response to M‐chlorophenylpiperazine in monkeys previously treated with 3,4‐methylenedioxymethamphetamine (MDMA) or fenfluramine

Cited by 14 publications

References 35 publications

Endocrine and Neurochemical Effects of 3,4-Methylenedioxymethamphetamine and Its Stereoisomers in Rhesus Monkeys

Endocrine and Neurochemical Effects of 3,4-Methylenedioxymethamphetamine and Its Stereoisomers in Rhesus Monkeys

Acute and long-term effects of MDMA on cerebral dopamine biochemistry and function

The Neuropsychopharmacology and Toxicology of 3,4‐methylenedioxy‐N‐ethyl‐amphetamine (MDEA)

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