Profile of MDMA Self-Administration from a Large Cohort of Rats: MDMA Develops a Profile of Dependence with Extended Testing

Schenk, Susan; Colussi-Mas, Joyce; Do, Jennifer; Bird, Judith

doi:10.4303/jdar/235602

Cited by 32 publications

(49 citation statements)

References 45 publications

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“…Additional IVSA studies with rhesus monkeys and baboons also revealed similar weak-to-moderate reinforcing properties [36,37]. Later studies by Schenk et al found that in a subset of rats, MDMA could support higher rates of self-administration than those observed in earlier reports [30,38,39], corroborating reports in humans that compulsive use is possible in certain individuals [40]. When compared to the collective results from these studies of MDMA self-administration, methylone appears to support more robust self-administration responding than does MDMA, albeit with a rightward shift in the inverted dose-effect curve.…”

Section: Discussionmentioning

confidence: 76%

“…Thus, at the higher doses, a larger percentage of rats acquired methylone IVSA in 2 hr daily sessions than rats self-administering MDMA in 6 hr daily access sessions (i.e., 60% for both the 0.25 mg/kg/infusion and 1 mg/kg/infusion MDMA dose groups) using nearly identical acquisition criterion (>10 lever presses per session) [30]. More recent work by Schenk and colleagues revealed that across 25 days of 2 hr IVSA sessions MDMA (1.0 mg/kg/infusion), only 49% (63 of 128 rats) acquired a total of ≥ 90 infusions across experimental sessions [39]. The present study revealed that only 5 rats failed to accumulate ≥ 90 infusions by the end of session 21, with 3 of those rats being in the 0.05 mg/kg group, 1 in the 0.1 mg/kg group, 1 in the 0.2 mg/kg group, and 0 in the 0.5 mg/kg group (data not shown).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Reinforcing and Rewarding Effects of Methylone, a Synthetic Cathinone Commonly Found in “Bath Salts”

Watterson

Hood

Sewalia³

et al. 2013

J Addict Res Ther

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Methylone is a member of the designer drug class known as synthetic cathinones which have become increasingly popular drugs of abuse in recent years. Commonly referred to as “bath salts”, these amphetamine-like compounds are sold as “legal” alternatives to illicit drugs such as cocaine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy). Following their dramatic rise in popularity along with numerous reports of toxicity and death, several of these drugs were classified as Schedule I drugs in the United States in 2012. Despite these bans, these drugs and other new structurally similar analogues continue to be abused. Currently, however, it is unknown whether these compounds possess the potential for compulsive use and addiction. The present study sought to determine the relative abuse liability of methylone by employing intravenous self-administration (IVSA) and intracranial self-stimulation (ICSS) paradigms in rats. We demonstrate that methylone (0.05, 0.1, 0.2, and 0.5 mg/kg/infusion) dose-dependently functions as a reinforcer, and that there is a significant positive relationship between methylone dose and reinforcer efficacy. Furthermore, responding during short access sessions (ShA, 2 hr/day) appeared more robust than previous IVSA studies with MDMA. However, unlike previous findings with abused stimulants such as cocaine or methamphetamine, long access sessions (LgA, 6 hr/day) did not lead to escalated drug intake or increased reinforcer efficacy. Finally, methylone produced a dose-dependent, but statistically non-significant, trend towards reductions in ICSS thresholds. Together these results reveal that methylone may possess an addiction potential similar to or greater than MDMA, yet patterns of self-administration and effects on brain reward function suggest that this drug may have a lower potential for abuse and compulsive use than prototypical psychostimulants.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

The Reinforcing and Rewarding Effects of Methylone, a Synthetic Cathinone Commonly Found in “Bath Salts”

Watterson

Hood

Sewalia³

et al. 2013

J Addict Res Ther

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“…Since we used the most behaviorally effective dose used in that prior paper, it is unlikely that training dose explains the difference. The MDMA IVSA data are the first available for female rats, but the diverse outcome in prior studies using male rats (Ball et al, 2007; Dalley et al, 2007; De La Garza et al, 2007; Feduccia et al, 2010; Schenk et al, 2012; Schenk et al, 2007) makes it impossible to determine whether sex differences are apparent.…”

Section: Discussionmentioning

confidence: 99%

Intravenous self-administration of mephedrone, methylone and MDMA in female rats

2015

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Male rats will intravenously self-administer (IVSA) the substituted cathinone stimulants (“bath salts”) mephedrone (4-methylmethcathione) and methylone (3,4-methylenedioxymethcathinone) robustly, whereas the IVSA of 3,4-methylenedioxymethamphetamine (MDMA) is inconsistent in many rat models. There are no data available on the self-administration of these drugs in female rats, thus a study was undertaken to contrast them directly. Groups of female Wistar rats were trained to self-administer mephedrone, methylone or MDMA (0.5 mg/kg/inf) under a Fixed-Ratio (FR) 1 schedule of reinforcement for 14 sessions. Following the acquisition interval, animals were evaluated in FR (0.0, 0.125, 0.25, 0.5, 1.0, 2.5 mg/kg/inf) and PR (0.125, 1.0 mg/kg/inf) dose-substitution procedures. The results show that female rats acquired the self-administration of all three compounds with intakes in mephedrone-trained rats that were significantly higher than that of methylone-trained or MDMA-trained rats. In dose-substitution under either FR or PR contingencies, however, the potencies of all three drugs were similar within the original training groups. The mephedrone-trained animals exhibited higher intakes of all drugs during dose-substitution, indicating lasting consequences of the training drug. Abuse liability of these three compounds is therefore predicted to be similar in established stimulant users but may differ in liability if they are primary drugs of initiation.

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“…This approach was taken so that learning of the operant response (selective lever pressing to obtain a reward) was not confounded with the reinforcer efficacy of MDMA. The training dose was selected based on the protocol of the lab that has produced the most MDMA IVSA to date [59]. Animals remained in the operant chamber for an additional hour after the end of the SA session (levers retracted) to fully characterize the body temperature response.…”

Section: Methodsmentioning

confidence: 99%

High ambient temperature facilitates the acquisition of 3,4-methylenedioxymethamphetamine (MDMA) self-administration

Aarde

Huang

Taffe

2017

Pharmacology Biochemistry and Behavior

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Rationale MDMA alters body temperature in rats with a direction that depends on the ambient temperature (TA). The thermoregulatory effects of MDMA and TA may affect intravenous self-administration (IVSA) of MDMA but limited prior reports conflict. Objective To determine how body temperature responses under high and low TA influence MDMA IVSA. Methods Male Sprague-Dawley rats were trained to IVSA MDMA (1.0 mg/kg/infusion; 2-hr sessions; FR5 schedule of reinforcement) under TA 20°C or 30°C. Radiotelemetry transmitters recorded body temperature and activity during IVSA. Results MDMA intake increased under both TA during acquisition, but to a greater extent in the 30°C group. The magnitude of hypothermia was initially equivalent between groups but diminished over training in the 30°C group. Within-session activity was initially lower in the 30° C group, but by the end of acquisition and maintenance, activity was similar for both groups. When TA conditions were swapped, the hot-trained group increased MDMA IVSA under 20 °C TA and a modest decrease in drug intake was observed in the cold-trained group under 30 °C TA. Subsequent non-contingent MDMA (1.0–5.0 mg/kg, i.v.) found that rats with higher MDMA IVSA rates showed blunted hypothermia compared with rats with lower IVSA levels; however, within-session activity did not differ by group. High TA increased intracranial self-stimulation thresholds in a different group of rats and MDMA reduced thresholds below baseline at low, but not high, TA. Conclusions High TA appears to enhance acquisition of MDMA IVSA through an aversive effect and not via thermoregulatory motivation.

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Profile of MDMA Self-Administration from a Large Cohort of Rats: MDMA Develops a Profile of Dependence with Extended Testing

Cited by 32 publications

References 45 publications

The Reinforcing and Rewarding Effects of Methylone, a Synthetic Cathinone Commonly Found in “Bath Salts”

The Reinforcing and Rewarding Effects of Methylone, a Synthetic Cathinone Commonly Found in “Bath Salts”

Intravenous self-administration of mephedrone, methylone and MDMA in female rats

High ambient temperature facilitates the acquisition of 3,4-methylenedioxymethamphetamine (MDMA) self-administration

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