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Differential substitution for the discriminative stimulus effects of 3,4-methylenedioxymethamphetamine and methylphenidate in rats.
J Pharmacol Exp Ther. 2014 Aug; 350(2):403-11.JP

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.

Authors+Show Affiliations

Department of Toxicology (T.M., N.U., H.K., H.W., A.M., M.S., T.S.) and Institute of Medicinal Chemistry (K.H.), Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan; and Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan (K.Y.).Department of Toxicology (T.M., N.U., H.K., H.W., A.M., M.S., T.S.) and Institute of Medicinal Chemistry (K.H.), Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan; and Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan (K.Y.).Department of Toxicology (T.M., N.U., H.K., H.W., A.M., M.S., T.S.) and Institute of Medicinal Chemistry (K.H.), Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan; and Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan (K.Y.).Department of Toxicology (T.M., N.U., H.K., H.W., A.M., M.S., T.S.) and Institute of Medicinal Chemistry (K.H.), Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan; and Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan (K.Y.).Department of Toxicology (T.M., N.U., H.K., H.W., A.M., M.S., T.S.) and Institute of Medicinal Chemistry (K.H.), Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan; and Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan (K.Y.).Department of Toxicology (T.M., N.U., H.K., H.W., A.M., M.S., T.S.) and Institute of Medicinal Chemistry (K.H.), Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan; and Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan (K.Y.).Department of Toxicology (T.M., N.U., H.K., H.W., A.M., M.S., T.S.) and Institute of Medicinal Chemistry (K.H.), Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan; and Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan (K.Y.).Department of Toxicology (T.M., N.U., H.K., H.W., A.M., M.S., T.S.) and Institute of Medicinal Chemistry (K.H.), Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan; and Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan (K.Y.).Department of Toxicology (T.M., N.U., H.K., H.W., A.M., M.S., T.S.) and Institute of Medicinal Chemistry (K.H.), Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan; and Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan (K.Y.) suzuki@hoshi.ac.jp.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24917544

Citation

Mori, Tomohisa, et al. "Differential Substitution for the Discriminative Stimulus Effects of 3,4-methylenedioxymethamphetamine and Methylphenidate in Rats." The Journal of Pharmacology and Experimental Therapeutics, vol. 350, no. 2, 2014, pp. 403-11.
Mori T, Uzawa N, Kazawa H, et al. Differential substitution for the discriminative stimulus effects of 3,4-methylenedioxymethamphetamine and methylphenidate in rats. J Pharmacol Exp Ther. 2014;350(2):403-11.
Mori, T., Uzawa, N., Kazawa, H., Watanabe, H., Mochizuki, A., Shibasaki, M., Yoshizawa, K., Higashiyama, K., & Suzuki, T. (2014). Differential substitution for the discriminative stimulus effects of 3,4-methylenedioxymethamphetamine and methylphenidate in rats. The Journal of Pharmacology and Experimental Therapeutics, 350(2), 403-11. https://doi.org/10.1124/jpet.114.214288
Mori T, et al. Differential Substitution for the Discriminative Stimulus Effects of 3,4-methylenedioxymethamphetamine and Methylphenidate in Rats. J Pharmacol Exp Ther. 2014;350(2):403-11. PubMed PMID: 24917544.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential substitution for the discriminative stimulus effects of 3,4-methylenedioxymethamphetamine and methylphenidate in rats. AU - Mori,Tomohisa, AU - Uzawa,Naoki, AU - Kazawa,Haruyo, AU - Watanabe,Hirohiko, AU - Mochizuki,Ayano, AU - Shibasaki,Masahiro, AU - Yoshizawa,Kazumi, AU - Higashiyama,Kimio, AU - Suzuki,Tsutomu, Y1 - 2014/06/10/ PY - 2014/6/12/entrez PY - 2014/6/12/pubmed PY - 2014/8/27/medline SP - 403 EP - 11 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 350 IS - 2 N2 - 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. SN - 1521-0103 UR - https://www.unboundmedicine.com/medline/citation/24917544/Differential_substitution_for_the_discriminative_stimulus_effects_of_34_methylenedioxymethamphetamine_and_methylphenidate_in_rats_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=24917544 DB - PRIME DP - Unbound Medicine ER -