The effect of long-term repeated exposure to 3,4-methylenedioxymethamphetamine on cardiovascular and thermoregulatory changes

Jaehne, Emily J.; Salem, Abdallah; Irvine, Rodney J.

doi:10.1007/s00213-008-1258-9

Cited by 14 publications

(17 citation statements)

References 41 publications

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“…These findings are in agreement with our previous work [63] and are consistent in principle to experiments showing the thermal response to MDMA (hyperthermia) occurs only after the first weekly injection of a multiple week treatment regimen [16]. MDMA-induced disruptions in thermoregulation have also been shown to persist after repeated MDMA administration [33,39]. However, different methodologies, such as mode of MDMA administration, dosage and schedule, are likely to account for variations in thermal responses to MDMA across studies.…”

Section: Discussionsupporting

confidence: 92%

“…Tolerance to the subjective effects of Ecstasy has been described by experienced users, who also report taking 5–10 times more MDMA pills in a single session than novice users [56]. Data from experimental animals reveal that tolerance develops to a number of MDMA-mediated responses after repeated MDMA administration, including hormone secretions, heart rate and 5-HT responses [6,39]. These findings exemplify the wide range of neuroadaptations produced by MDMA exposure.…”

Section: Introductionmentioning

confidence: 99%

“…Animal models have shown that MDMA can produce hyperthermia or hypothermia depending on ambient temperature [49,53], and involvement of both central and peripheral mechanisms in MDMA-induced thermal dysregulation [34,71]. In addition, repeated MDMA administration has been reported to produce both sensitization- and tolerance-like effects on MDMA-induced core temperature disruption [32,39,60]. …”

Section: Introductionmentioning

confidence: 99%

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Behavioral, thermal and neurochemical effects of acute and chronic 3,4-methylenedioxymethamphetamine (“Ecstasy”) self-administration

Reverón

Maier

Duvauchelle

2010

Behavioural Brain Research

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Abstract3,4-methylenedioxymethamphetamine (MDMA) is a popular methamphetamine derivative associated with young adults and all-night dance parties. However, the enduring effects of MDMA at voluntary intake levels have not been extensively investigated. In this study, MDMA-influenced behaviors and core temperatures were assessed over the course of 20 daily MDMA selfadministration sessions in rats. In vivo microdialysis techniques were used in a subsequent MDMA challenge test session to determine extracellular nucleus accumbens dopamine (NAcc DA) and serotonin (5-HT) levels in MDMA-experienced and naïve animals before and after a selfadministered MDMA injection (3.0 mg/kg, i.v.). During self-administration sessions, gradual and significant increases in MDMA intake and MDMA-stimulated locomotor activity were observed across sessions. Core temperature significantly decreased during initial MDMA sessions, but was unaltered by the last 10 sessions. In the MDMA challenge test, MDMA-naïve rats showed significantly higher NAcc 5-HT responses compared to MDMA-experienced rats, though MDMA experience did not affect the magnitude of NAcc DA response. The overall findings suggest that changes in MDMA-induced responses over the course of increasing levels of drug exposure may reflect the development of tolerance to a number of MDMA effects.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Behavioral, thermal and neurochemical effects of acute and chronic 3,4-methylenedioxymethamphetamine (“Ecstasy”) self-administration

Reverón

Maier

Duvauchelle

2010

Behavioural Brain Research

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“…It is known that some tolerance or tachyphylaxis to the hyperthermic effect of certain psychostimulant drugs [13] can exist. We administered 4-MA at three different doses (2.5, 5 and 7.5 mg/Kg) four times in a 2 h interval in a normal ambient temperature.…”

Section: Effect Of Repeated Doses Of 4-mamentioning

confidence: 99%

Serotonin is involved in the psychostimulant and hypothermic effect of 4-methylamphetamine in rats

Rubio

López-Arnau

Piccoli

et al. 2015

Neuroscience Letters

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Abstract4-methylamphetamine (4-MA) has recently emerged as a designer drug of abuse in Europe and it is consumed always with amphetamine. There have been reported some deaths and non-fatal intoxications related to 4-MA. We investigated the changes in locomotor activity and body temperature after 4-MA administration to male SpragueDawley rats. Our experiments were carried out at a normal or high ambient temperature. 4-MA (2.5 -10 mg/Kg, given subcutaneously) increased, in a dosedependent manner, the horizontal locomotor activity that was significantly reduced by ketanserin, p-cholorophenylalanine (pCPA) or haloperidol. In addition, we have studied the effect of 4-MA on core body temperature by means of an implanted electronic thermograph, enabling continuous measurement of body temperature. We observed a dose-dependent hypothermic response to 4-MA that reached a maximum 45 min after a single injection. We also evidenced slight tachyphylaxis to the hypothermic effect when 4-MA was administered four times in a 2 h interval. The pre-treatment of animals with pCPA or pindolol, but not with ketanserin, fully abolished the hypothermic effect of 4-MA. With all that, we conclude that hypothermia induced by 4-MA is due to the release of 5-HT which activates postsynaptic 5-HT 1A receptors.

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“…Much of the research regarding the adverse consequences of MDMA use has focused on mood 11,13 and thermoregulation 14,15 . However, changes in 5‐HT function are also of concern in the context of sleep given the pivotal role that 5‐HT plays in sleep and circadian rhythm regulation 16,17 .…”

Section: Sleep Variables In Human Ecstasy Usersmentioning

confidence: 99%

Ecstasy and sleep disturbance: Progress towards elucidating a role for the circadian system

Ogeil

Rajaratnam

Broadbear

2011

Sleep and Biological Rhythms

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MDMA (ecstasy) is an illicit drug which has pharmacological actions on the serotonin system, leading to a number of physiological and behavioral changes. Research conducted in both animals and humans has focused on how ecstasy use affects systems or functions in which serotonin has a regulatory role including mood, sleep and circadian rhythms. In this paper we review the evidence with respect to changes in sleep and circadian rhythms following ecstasy use. Studies of the subjective measurement of sleep have suggested that there are changes in sleep quality and duration following ecstasy use, while research utilizing objective measures including polysomnography has highlighted changes in sleep architecture following ecstasy use. Collectively these findings suggest that there are consequences associated with ecstasy use, and the implications of these findings for ecstasy users will be examined. Finally, preliminary evidence from the animal literature implicating ecstasy as having specific effects on the circadian system will be reviewed. A discussion of the limitations of the current evidence for such a claim is presented, and possible directions for future research are explored.

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The effect of long-term repeated exposure to 3,4-methylenedioxymethamphetamine on cardiovascular and thermoregulatory changes

Abstract: Long-term treatment with MDMA resulted in apparent tolerance to the effects of the drug on HR, dysregulation of TC in thermal gradient, and depletion of cortical DOPAC and 5-HIAA.

Cited by 14 publications

References 41 publications

Behavioral, thermal and neurochemical effects of acute and chronic 3,4-methylenedioxymethamphetamine (“Ecstasy”) self-administration

Behavioral, thermal and neurochemical effects of acute and chronic 3,4-methylenedioxymethamphetamine (“Ecstasy”) self-administration

Serotonin is involved in the psychostimulant and hypothermic effect of 4-methylamphetamine in rats

Ecstasy and sleep disturbance: Progress towards elucidating a role for the circadian system

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