Elevation of Ambient Room Temperature has Differential Effects on MDMA-Induced 5-HT and Dopamine Release in Striatum and Nucleus Accumbens of Rats

O’Shea, Esther; Escobedo, Isabel; Orío, Laura; Sánchez, Verónica; Navarro, Miguel; Green, A Richard; Colado, M. Isabel

doi:10.1038/sj.npp.1300673

Cited by 72 publications

(63 citation statements)

References 51 publications

(50 reference statements)

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“…Previous studies have shown that the thermoregulatory effects of MDMA depend critically on ambient temperature, with the same doses of MDMA eliciting hypothermia at low ambient temperatures, and hyperthermia at high ambient temperatures (Dafters, 1994;Malberg and Seiden, 1998). Importantly, the locomotor-stimulant effects of MDMA are not affected by ambient temperature (Dafters, 1994;O'Shea et al, 2005). Similarly, the structurally similar synthetic cathinone 4-MMC has recently been shown to exhibit thermoregulatory and locomotor effects distinct from those of MDMA or METH (Wright et al, 2012), suggesting that an evaluation of the role of ambient temperature in MDPV effects is warranted.…”

Section: Introductionmentioning

confidence: 89%

“…Because ambient temperature has been shown to largely affect the thermoregulatory effects of MDMA (Dafters, 1994;Malberg and Seiden, 1998)-but not to alter locomotorstimulant effects (Dafters, 1994;O'Shea et al, 2005)-we used radiotelemetry to simultaneously monitor both of these end points in response to various doses of MDPV at either 20 or 28 1C. Interestingly, we found that, in contrast to MDMA, locomotor-stimulant effects of 10 mg/kg MDPV were enhanced at the warm ambient temperature.…”

Section: 4-methylenedioxypyrovalerone In Micementioning

confidence: 99%

See 1 more Smart Citation

In vivo Effects of Abused ‘Bath Salt’ Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity

Fantegrossi

Gannon

Zimmerman

et al. 2012

Neuropsychopharmacol

138

151

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In recent years, synthetic analogues of naturally occurring cathinone have emerged as psychostimulant-like drugs of abuse in commercial 'bath salt' preparations. 3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of these illicit products, and its structural similarities to the more well-known drugs of abuse 3,4-methylenedioxymethamphetamine (MDMA), and methamphetamine (METH) suggest that it may have similar in vivo effects to these substances. In these studies, adult male NIH Swiss mice were trained to discriminate 0.3 mg/kg MDPV from saline, and the interoceptive effects of a range of substitution doses of MDPV, MDMA, and METH were then assessed. In separate groups of mice, surgically implanted radiotelemetry probes simultaneously monitored thermoregulatory and locomotor responses to various doses of MDPV and MDMA, as a function of ambient temperature. We found that mice reliably discriminated the MDPV training dose from saline and that cumulative doses of MDPV, MDMA, and METH fully substituted for the MDPV training stimulus. All three drugs had similar ED 50 values in this procedure. Stimulation of motor activity was observed following administration of a wide range of MDPV doses (1-30 mg/kg), and the warm ambient temperature potentiated motor activity and elicited profound stereotypy and self-injurious behavior at 30 mg/kg. In contrast, MDPV-induced hyperthermic effects were observed in only the warm ambient environment. This pattern of effects is in sharp contrast to MDMA, where ambient temperature interacts with thermoregulation, but not locomotor activity. These studies suggest that although the interoceptive effects of MDPV are similar to those of MDMA and METH, direct effects on thermoregulatory processes and locomotor activity are likely mediated by different mechanisms than those of MDMA.

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Section: Introductionmentioning

confidence: 89%

Section: 4-methylenedioxypyrovalerone In Micementioning

confidence: 99%

In vivo Effects of Abused ‘Bath Salt’ Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity

Fantegrossi

Gannon

Zimmerman

et al. 2012

Neuropsychopharmacol

138

151

View full text Add to dashboard Cite

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“…These investigators demonstrated that the increase in the extracellular concentration of DA, as well as 5-HT, in the n. accumbens, but not striatum, is greater at 30° C than at 20°C. On the basis of these results, O'Shea et al (2005) have suggested that the rewarding properties of MDMA may be more pronounced at higher ambient temperatures (O'Shea et al, 2005).…”

Section: Nucleusmentioning

confidence: 98%

“…Finally, O'Shea and coworkers have investigated the influence of ambient temperature on MDMA-induced DA and 5-HT release in the n. accumbens and striatum (O'Shea et al, 2005). These investigators demonstrated that the increase in the extracellular concentration of DA, as well as 5-HT, in the n. accumbens, but not striatum, is greater at 30° C than at 20°C.…”

Section: Nucleusmentioning

confidence: 99%

Actions of 3,4-methylenedioxymethamphetamine (MDMA) on cerebral dopaminergic, serotonergic and cholinergic neurons

Gudelsky

Yamamoto

2008

Pharmacology Biochemistry and Behavior

120

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Abstract3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative and a popular drug of abuse that exhibits mild hallucinogenic and rewarding properties and engenders feelings of connectedness and openness. The unique psychopharmacological profile of this drug of abuse most likely is derived from the property of MDMA to promote the release of dopamine and serotonin (5-HT) in multiple brain regions. The present review highlights primarily data from studies employing in vivo microdialysis that detail the actions of MDMA on the release of these neurotransmitters. Data from in vivo microdialysis experiments indicate that MDMA, like most amphetamine derivatives, increases the release of dopamine in the striatum, n. accumbens and prefrontal cortex. However, the release of dopamine evoked by MDMA in each of these brain regions appears to be modulated by concomitantly released 5-HT and the subsequent activation of 5-HT2A/C or 5-HT2B/C receptors. In addition to its stimulatory effect on the release of monoamines, MDMA also enhances the release of acetylcholine in the striatum, hippocampus and prefrontal cortex, and this cholinergic response appears to be secondary to the activation of histaminergic, dopaminergic and/or serotonergic receptors. Beyond the acute stimulatory effect of MDMA on neurotransmitter release, MDMA also increases the extracellular concentration of energy substrates, e.g., glucose and lactate in the brain. In contrast to the acute stimulatory actions of MDMA on the release of monoamines and acetylcholine, the repeated administration of high doses of MDMA is thought to result in a selective neurotoxicity to 5-HT axon terminals in the rat. Additional studies are reviewed that focus on the alterations in neurotransmitter responses to pharmacological and physiological stimuli that accompany MDMA-induced 5-HT neurotoxicity.

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“…MDMA induces the presynaptic release of dopamine (DA) and serotonin (5-HT) in rats (Gough et al, 1991;Hiramatsu and Cho, 1990;Kankaanpaa et al, 1998;Koch and Galloway, 1997;Schmidt et al, 1987;Yamamoto and Spanos, 1988) and raises extracellular DA and 5-HT in the nucleus accumbens (Nacc) (Kankaanpaa et al, 1998;O'Shea et al, 2005;White et al, 1994), increasing preferentially DA transmission in the shell compared to the core of Nacc (Cadoni et al, 2005). MDMA also produces a stimulatory effect on the release of acetylcholine in the rat prefrontal cortex, striatum, and dorsal hippocampus (Acquas et al, 2001;Nair and Gudelsky, 2006).…”

Section: Introductionmentioning

confidence: 99%

Rewarding Effects and Reinstatement of MDMA-Induced CPP in Adolescent Mice

Daza-Losada

Couto

Manzanedo

et al. 2007

Neuropsychopharmacol

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Although the rewarding effects of 3,4-methylenedioxy-metamphetamine (MDMA) have been demonstrated in self-administration and conditioned place preference (CPP) procedures, its addictive potential (ie, the vulnerability to relapse, measured by its ability to induce reinstatement of an extinguished response), remains poorly understood. In this study, the effects of MDMA (5, 10, and 20 mg/kg) on the acquisition, extinction and reinstatement of CPP were evaluated in mice, using two different protocols during acquisition of CPP. In the first experiment, animals were trained using a two-session/day schedule (MDMA and saline for 4 consecutive days), whereas in the second experiment, they were trained using an alternating day schedule (MDMA and saline each 48 h). After extinction, the ability of drug priming to reinstate CPP was evaluated. In Experiment 1, MDMA did not significantly increase the time spent in the drug-paired compartment during the post-conditioning (Post-C) test, although the preference was evident a week afterwards, lasting between 2 and 21 weeks. No reinstatement was observed after MDMA priming. In Experiment 2, all doses produced CPP in Post-C, which lasted between 1 and 4 weeks. MDMA induces reinstatement at doses up to 4 times lower than those used in conditioning. The analyses of brain monoamines revealed that the daily schedule of treatment induces a non-dose-dependent decrease in dopamine and serotonin (5-HT) in the striatum, whereas the alternating schedule produces a dose-dependent decrease of 5-HT in the cortex. These results demonstrate that MDMA produces long-lasting rewarding effects and reinstatement after extinction, suggesting the susceptibility of this drug to induce addiction.

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Elevation of Ambient Room Temperature has Differential Effects on MDMA-Induced 5-HT and Dopamine Release in Striatum and Nucleus Accumbens of Rats

Cited by 72 publications

References 51 publications

In vivo Effects of Abused ‘Bath Salt’ Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity

In vivo Effects of Abused ‘Bath Salt’ Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity

Actions of 3,4-methylenedioxymethamphetamine (MDMA) on cerebral dopaminergic, serotonergic and cholinergic neurons

Rewarding Effects and Reinstatement of MDMA-Induced CPP in Adolescent Mice

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