Differential substitution for the discriminative stimulus effects of 3,4-methylenedioxymethamphetamine and methylphenidate in rats.
Tomohisa Mori, Naoki Uzawa, Haruyo Kazawa, Hirohiko Watanabe, Ayano Mochizuki, Masahiro Shibasaki, Kazumi Yoshizawa, Kimio Higashiyama, Tsutomu Suzuki
Journal of Pharmacology and Experimental Therapeutics August 2014 DOI: 10.1124/jpet.114.214288 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal drug discrimination study Peer reviewed |
|---|---|
| Population | Rats trained to discriminate MDMA or methylphenidate from saline |
| Interventions | MDMA methylphenidate methamphetamine ephedrine bupropion |
| Dose | MDMA 2.5 mg/kg, methylphenidate 5.0 mg/kg |
| Topics | MDMA |
| Key points | MDMA and methylphenidate did not cross-substitute for each other in rats. Methamphetamine, ephedrine, and bupropion substituted for methylphenidate but not MDMA, while 5-HT1A and 5-HT2 agonists fully substituted for MDMA. The authors argue that noradrenergic and dopaminergic activation is important for methylphenidate's discriminative stimulus effects, whereas serotonergic activation is crucial for MDMA's, indicating these effects are distinct. |
Abstract
Previous studies have demonstrated that methylphenidate, MDMA (3,4-methylenedioxymethamphetamine), and other psychostimulants exert stimulant-like subjective effects in humans. Furthermore, MDMA and methylphenidate substitute for the discriminative stimulus effects of psychostimulants, such as amphetamine and cocaine, in animals, which suggests that MDMA and methylphenidate may produce similar discriminative stimulus effects in rats. However, there is no evidence regarding the similarities between the discriminative stimulus effects of MDMA and methylphenidate. To explore this issue, cross-substitution, substitution, and combination tests were conducted in rats that had been trained to discriminate between MDMA (2.5 mg/kg) or methylphenidate (5.0 mg/kg) and saline. In the cross-substitution tests, MDMA and methylphenidate did not cross-substitute for each other. In the substitution test, methamphetamine substituted for the discriminative stimulus effects of methylphenidate, but not for those of MDMA. Furthermore, ephedrine and bupropion, which activate dopaminergic and noradrenergic systems, substituted for the discriminative stimulus effects of methylphenidate. On the other hand, serotonin (5-HT) receptor agonists 5-HT1A and 5-HT2 fully substituted for the discriminative stimulus effects of MDMA. These results suggest that activation of the noradrenergic and dopaminergic systems is important for the discriminative stimulus effects of methylphenidate, whereas activation of the serotonergic system is crucial for the discriminative stimulus effects of MDMA. Even though MDMA, like psychostimulants, exerts stimulant-like effects, our findings clearly indicate that the discriminative stimulus effects of MDMA are distinctly different from those of other psychostimulants in rats.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 9
- Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine ACS Chemical Neuroscience July 12, 2018
- Dopamine and serotonin antagonists fail to alter the discriminative stimulus properties of ±methylenedioxymethamphetamine Behavioural Pharmacology June 1, 2019
- Possible Involvement of Hallucinogenic Effects in the Aversive Effects Induced by Kappa‐Opioid and 5‐ HT 2A / 2C Receptor Agonists in Mice Neuropsychopharmacology Reports November 23, 2025
- Enhancement of the rewarding effects of 3,4-methylenedioxymethamphetamine in orexin knockout mice. Behavioural Brain Research July 9, 2020
- In vivo effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated form in rodents: Drug discrimination and thermoregulation. Drug and Alcohol Dependence January 13, 2020
and 4 more in the library
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