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High levels of intravenous mephedrone (4-methylmethcathinone) self-administration in rats: neural consequences and comparison with methamphetamine.
J Psychopharmacol. 2013 Sep; 27(9):823-36.JP

Abstract

Mephedrone (MMC) is a relatively new recreational drug that has rapidly increased in popularity in recent years. This study explored the characteristics of intravenous MMC self-administration in the rat, with methamphetamine (METH) used as a comparator drug. Male Sprague-Dawley rats were trained to nose poke for intravenous MMC or METH in daily 2 h sessions over a 10 d acquisition period. Dose-response functions were then established under fixed- and progressive-ratio (FR and PR) schedules over three subsequent weeks of testing. Brains were analyzed ex vivo for striatal serotonin (5-HT) and dopamine (DA) levels and metabolites, while autoradiography assessed changes in the regional density of 5-HT and serotonin transporter (SERT) and DA transporter (DAT) and induction of the inflammation marker translocator protein (TSPO). Results showed that MMC was readily and vigorously self-administered via the intravenous route. Under a FR1 schedule, peak responding for MMC was obtained at 0.1 mg/kg/infusion, versus 0.01 mg/kg/infusion for METH. Break points under a PR schedule peaked at 1 mg/kg/infusion MMC versus 0.3 mg/kg/infusion for METH. Final intakes of MMC were 31.3 mg/kg/d compared to 4 mg/kg/d for METH. Rats self-administering MMC, but not METH, gained weight at a slower rate than control rats. METH, but not MMC, self-administration elevated TSPO receptor density in the nucleus accumbens and hippocampus, while MMC, but not METH, self-administration decreased striatal 5-hydroxyindolacetic acid (5-HIAA) concentrations. In summary, MMC supported high levels of self-administration, matching or exceeding those previously reported with other drugs of abuse.

Authors+Show Affiliations

School of Psychology, University of Sydney, Sydney, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

23739178

Citation

Motbey, Craig P., et al. "High Levels of Intravenous Mephedrone (4-methylmethcathinone) Self-administration in Rats: Neural Consequences and Comparison With Methamphetamine." Journal of Psychopharmacology (Oxford, England), vol. 27, no. 9, 2013, pp. 823-36.
Motbey CP, Clemens KJ, Apetz N, et al. High levels of intravenous mephedrone (4-methylmethcathinone) self-administration in rats: neural consequences and comparison with methamphetamine. J Psychopharmacol (Oxford). 2013;27(9):823-36.
Motbey, C. P., Clemens, K. J., Apetz, N., Winstock, A. R., Ramsey, J., Li, K. M., Wyatt, N., Callaghan, P. D., Bowen, M. T., Cornish, J. L., & McGregor, I. S. (2013). High levels of intravenous mephedrone (4-methylmethcathinone) self-administration in rats: neural consequences and comparison with methamphetamine. Journal of Psychopharmacology (Oxford, England), 27(9), 823-36. https://doi.org/10.1177/0269881113490325
Motbey CP, et al. High Levels of Intravenous Mephedrone (4-methylmethcathinone) Self-administration in Rats: Neural Consequences and Comparison With Methamphetamine. J Psychopharmacol (Oxford). 2013;27(9):823-36. PubMed PMID: 23739178.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High levels of intravenous mephedrone (4-methylmethcathinone) self-administration in rats: neural consequences and comparison with methamphetamine. AU - Motbey,Craig P, AU - Clemens,Kelly J, AU - Apetz,Nadine, AU - Winstock,Adam R, AU - Ramsey,John, AU - Li,Kong M, AU - Wyatt,Naomi, AU - Callaghan,Paul D, AU - Bowen,Michael T, AU - Cornish,Jennifer L, AU - McGregor,Iain S, Y1 - 2013/06/05/ PY - 2013/6/7/entrez PY - 2013/6/7/pubmed PY - 2014/4/9/medline KW - Mephedrone KW - addiction KW - autoradiography KW - neurotoxicity KW - self-administration SP - 823 EP - 36 JF - Journal of psychopharmacology (Oxford, England) JO - J. Psychopharmacol. (Oxford) VL - 27 IS - 9 N2 - Mephedrone (MMC) is a relatively new recreational drug that has rapidly increased in popularity in recent years. This study explored the characteristics of intravenous MMC self-administration in the rat, with methamphetamine (METH) used as a comparator drug. Male Sprague-Dawley rats were trained to nose poke for intravenous MMC or METH in daily 2 h sessions over a 10 d acquisition period. Dose-response functions were then established under fixed- and progressive-ratio (FR and PR) schedules over three subsequent weeks of testing. Brains were analyzed ex vivo for striatal serotonin (5-HT) and dopamine (DA) levels and metabolites, while autoradiography assessed changes in the regional density of 5-HT and serotonin transporter (SERT) and DA transporter (DAT) and induction of the inflammation marker translocator protein (TSPO). Results showed that MMC was readily and vigorously self-administered via the intravenous route. Under a FR1 schedule, peak responding for MMC was obtained at 0.1 mg/kg/infusion, versus 0.01 mg/kg/infusion for METH. Break points under a PR schedule peaked at 1 mg/kg/infusion MMC versus 0.3 mg/kg/infusion for METH. Final intakes of MMC were 31.3 mg/kg/d compared to 4 mg/kg/d for METH. Rats self-administering MMC, but not METH, gained weight at a slower rate than control rats. METH, but not MMC, self-administration elevated TSPO receptor density in the nucleus accumbens and hippocampus, while MMC, but not METH, self-administration decreased striatal 5-hydroxyindolacetic acid (5-HIAA) concentrations. In summary, MMC supported high levels of self-administration, matching or exceeding those previously reported with other drugs of abuse. SN - 1461-7285 UR - https://www.unboundmedicine.com/medline/citation/23739178/High_levels_of_intravenous_mephedrone__4_methylmethcathinone__self_administration_in_rats:_neural_consequences_and_comparison_with_methamphetamine_ L2 - http://journals.sagepub.com/doi/full/10.1177/0269881113490325?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -