Estimating the relative reinforcing strength of (±)-3,4-methylenedioxymethamphetamine (MDMA) and its isomers in rhesus monkeys: comparison to (+)-methamphetamine

Wang, Zhixia; Woolverton, William L.

doi:10.1007/s00213-006-0599-5

Cited by 60 publications

(74 citation statements)

References 28 publications

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“…For example, under FR schedules of reinforcement the peak of the MDMA dose-response curve in monkeys was 0.03 mg/kg/inj (Beardsley et al 1986;Lamb and Griffiths 1987;Fantegrossi et al 2002). In contrast, this dose of MDMA failed to maintain behavior above vehicle levels under progressive-ratio (Lile et al 2005;Wang and Woolverton 2007) or concurrent (present study) schedules of reinforcement at 24°C. These results support the notion that measures of reinforcing effects and reinforcing strength do not provide identical information on reinforcement (cf.…”

Section: Discussioncontrasting

confidence: 50%

Effects of ambient temperature on the relative reinforcing strength of MDMA using a choice procedure in monkeys

et al. 2007

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Rationale-3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is frequently used in hot environments, such as rave parties. Studies in laboratory animals have shown that ambient temperature can alter the behavioral and neurochemical effects of MDMA.Objective-To examine the influence of ambient temperature on the relative reinforcing strength of MDMA and reinstatement of behavior previously maintained by MDMA. Methods-The effects of cool (18°C), room (24°C) and warm (31°C) temperatures were examined when MDMA was available under a concurrent fixed-ratio 30 schedule of MDMA (saline, 0.03-0.3 mg/kg/inj) and food choice in rhesus monkeys (n=5). During saline substitutions, the effect of noncontingent MDMA (0.03-0.3 mg/kg) on response allocation was examined at each ambient temperature.Results-At room temperature, MDMA choice increased as a function of dose, such that food was preferred over a low MDMA dose (0.03 mg/kg/inj) whereas higher doses were preferred over food. Elevating the ambient temperature significantly increased the relative reinforcing strength of 0.03 mg/kg/inj MDMA and lowering the ambient temperature significantly attenuated choice of 0.1 mg/ kg/inj MDMA. Noncontingent injections of MDMA administered before a session in which saline was the alternative to food dose-dependently increased injection-lever responding; this effect was not influenced by ambient temperature.Conclusions-These results suggest that ambient temperature can affect the relative reinforcing strength of MDMA, but not MDMA-induced reinstatement. Furthermore, these results suggest environmental strategies for decreasing the reinforcing strength of MDMA.

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Section: Discussioncontrasting

confidence: 50%

Effects of ambient temperature on the relative reinforcing strength of MDMA using a choice procedure in monkeys

et al. 2007

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“…Specifically, these studies support the notion that S(ϩ)-MDMA more readily functions as a psychomotor stimulant, whereas R(Ϫ)-MDMA more readily functions as a hallucinogen (Glennon et al, 1988;Baker et al, 1995;Murnane et al, 2009). This work has been further supported by studies showing that S(ϩ)-MDMA and S,R(Ϯ)-MDMA, but not R(Ϫ)-MDMA, functioned as locomotor stimulants (Fantegrossi et al, 2003) or positive reinforcers, under a progressive ratio schedule (Wang and Woolverton, 2007). Taken together, this literature suggests that the stereoisomers of MDMA have distinct behavioral and interoceptive effects.…”

mentioning

confidence: 59%

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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“…9A shows a positive correlation for 10 monoamine releasers between pharmacological selectivity (expressed as selectivity to release DA versus 5HT) and efficacy to facilitate ICSS (expressed as maximal increase in % baseline stimulations) (Bauer et al, 2013b). Moreover, and importantly for consideration ICSS in Abuse Potential Testing of abuse potential testing, previous studies with many of these same monoamine releasers had already shown a similar relationship between pharmacological selectivity to release DA versus 5HT and behavioral efficacy to reinforce drug self-administration under a progressive-ratio procedure in rhesus monkeys Wee et al, 2005;Wang and Woolverton, 2007). Accordingly, we also correlated efficacy of these monoamine releasers to facilitate ICSS with their efficacy to maintain self-administration in monkeys, and the resulting positive correlation is shown in Fig.…”

Section: Drug Effects On Intracranial Self-stimulation By Drug Cmentioning

confidence: 99%

“…The regression was significant (Pearson r = 0.89, R 2 = 0.78, P = 0.0006). B, Abscissa: Maximum break point maintained by any drug dose under a progressive-ratio schedule of drug self-administration in rhesus monkeys (Wee et al, 2005;Wang and Woolverton, 2007). Ordinate.…”

Section: Drug Effects On Intracranial Self-stimulation By Drug Cmentioning

confidence: 99%

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

2014

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Estimating the relative reinforcing strength of (±)-3,4-methylenedioxymethamphetamine (MDMA) and its isomers in rhesus monkeys: comparison to (+)-methamphetamine

Cited by 60 publications

References 28 publications

Effects of ambient temperature on the relative reinforcing strength of MDMA using a choice procedure in monkeys

Effects of ambient temperature on the relative reinforcing strength of MDMA using a choice procedure in monkeys

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

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

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