The Reinforcing and Rewarding Effects of Methylone, a Synthetic Cathinone Commonly Found in "Bath Salts" - PubMed (original) (raw)
The Reinforcing and Rewarding Effects of Methylone, a Synthetic Cathinone Commonly Found in "Bath Salts"
Lucas R Watterson et al. J Addict Res Ther. 2012.
Abstract
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.
Keywords: Intracranial self-stimulation; Methylone; Monoamine; Reinforcement; Reward; Self-administration; Stimulant.
Figures
Figure 1
Intravenous self-administration (IVSA) of methylone. Data presented are active and inactive lever presses across the first 21 days of IVSA sessions for the (a) 0.05 (b) 0.1 (c) 0.2 and (d) 0.5 mg/kg/infusion groups (n = 12 for 0.05 and 0.5 mg/kg/infusion groups; n = 11 for the 0.1 and 0.2 mg/kg/infusion groups). *p<0.05 between active and inactive lever presses.
Figure 2
(a) Total number of infusions obtained during the first 21 days of 2 hr daily access sessions for each dose of methylone tested (n=12 for 0.05 and 0.5 mg/kg/infusion groups; n = 11 for the 0.1 and 0.2 mg/kg/infusion groups). (b) Percent of animals at or above criterion (10 active lever presses per session) for each experimental session.
Figure 3
Total number of infusions earned during progressive ratio (PR) tests following 21 days of ShA sessions (ShA PR) and 10 days of LgA sessions (LgA PR) for the 0.05, 0.1, 0.2, and 0.5 mg/kg/infusion groups (n = 12 for 0.05 and 0.5 mg/kg/infusion groups; n = 11 for the 0.1 and 0.2 mg/kg/infusion groups). *p<0.05 compared to the 0.05, 0.1, and 0.2 mg/kg/infusion dose groups. (b) Total number of infusions obtained during the 10 days of LgA IVSA sessions for each dose of methylone tested (n=10 for 0.05 and 0.5 mg/kg/infusion groups; n = 11 for the 0.1 and 0.2 mg/kg/infusion groups).
Figure 4
Effects of saline vehicle and methylone (0.1, 0.5, 1, 3, 5, and 10 mg/kg, i.p.) on intracranial self-stimulation (ICSS) current-intensity thresholds (n=4).
Similar articles
- Intravenous self-administration of entactogen-class stimulants in male rats.
Vandewater SA, Creehan KM, Taffe MA. Vandewater SA, et al. Neuropharmacology. 2015 Dec;99:538-45. doi: 10.1016/j.neuropharm.2015.08.030. Epub 2015 Aug 21. Neuropharmacology. 2015. PMID: 26302654 Free PMC article. - Potent rewarding and reinforcing effects of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV).
Watterson LR, Kufahl PR, Nemirovsky NE, Sewalia K, Grabenauer M, Thomas BF, Marusich JA, Wegner S, Olive MF. Watterson LR, et al. Addict Biol. 2014 Mar;19(2):165-74. doi: 10.1111/j.1369-1600.2012.00474.x. Epub 2012 Jul 11. Addict Biol. 2014. PMID: 22784198 Free PMC article. - Effects of α-pyrrolidinopentiophenone and 4-methyl-N-ethylcathinone, two synthetic cathinones commonly found in second-generation "bath salts," on intracranial self-stimulation thresholds in rats.
Watterson LR, Burrows BT, Hernandez RD, Moore KN, Grabenauer M, Marusich JA, Olive MF. Watterson LR, et al. Int J Neuropsychopharmacol. 2014 Oct 31;18(1):pyu014. doi: 10.1093/ijnp/pyu014. Int J Neuropsychopharmacol. 2014. PMID: 25522379 Free PMC article. - Psychoactive "bath salts": not so soothing.
Baumann MH, Partilla JS, Lehner KR. Baumann MH, et al. Eur J Pharmacol. 2013 Jan 5;698(1-3):1-5. doi: 10.1016/j.ejphar.2012.11.020. Epub 2012 Nov 23. Eur J Pharmacol. 2013. PMID: 23178799 Free PMC article. Review. - Bath salts and synthetic cathinones: an emerging designer drug phenomenon.
German CL, Fleckenstein AE, Hanson GR. German CL, et al. Life Sci. 2014 Feb 27;97(1):2-8. doi: 10.1016/j.lfs.2013.07.023. Epub 2013 Aug 2. Life Sci. 2014. PMID: 23911668 Free PMC article. Review.
Cited by
- Behavioral pharmacology of designer cathinones: a review of the preclinical literature.
Gregg RA, Rawls SM. Gregg RA, et al. Life Sci. 2014 Feb 27;97(1):27-30. doi: 10.1016/j.lfs.2013.10.033. Epub 2013 Nov 11. Life Sci. 2014. PMID: 24231450 Free PMC article. Review. - Dissecting the Influence of Two Structural Substituents on the Differential Neurotoxic Effects of Acute Methamphetamine and Mephedrone Treatment on Dopamine Nerve Endings with the Use of 4-Methylmethamphetamine and Methcathinone.
Anneken JH, Angoa-Pérez M, Sati GC, Crich D, Kuhn DM. Anneken JH, et al. J Pharmacol Exp Ther. 2017 Mar;360(3):417-423. doi: 10.1124/jpet.116.237768. Epub 2016 Dec 30. J Pharmacol Exp Ther. 2017. PMID: 28039330 Free PMC article. - The synthetic cathinones, butylone and pentylone, are stimulants that act as dopamine transporter blockers but 5-HT transporter substrates.
Saha K, Li Y, Holy M, Lehner KR, Bukhari MO, Partilla JS, Sandtner W, Sitte HH, Baumann MH. Saha K, et al. Psychopharmacology (Berl). 2019 Mar;236(3):953-962. doi: 10.1007/s00213-018-5075-5. Epub 2018 Oct 22. Psychopharmacology (Berl). 2019. PMID: 30345459 Free PMC article. - "Ecstasy" to addiction: Mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA.
Dolan SB, Chen Z, Huang R, Gatch MB. Dolan SB, et al. Neuropharmacology. 2018 May 1;133:171-180. doi: 10.1016/j.neuropharm.2018.01.020. Epub 2018 Jan 31. Neuropharmacology. 2018. PMID: 29378213 Free PMC article. - Synthetic Cathinone and Cannabinoid Designer Drugs Pose a Major Risk for Public Health.
Weinstein AM, Rosca P, Fattore L, London ED. Weinstein AM, et al. Front Psychiatry. 2017 Aug 23;8:156. doi: 10.3389/fpsyt.2017.00156. eCollection 2017. Front Psychiatry. 2017. PMID: 28878698 Free PMC article. Review.
References
- Patel NB. Mechanism of action of cathinone: the active ingredient of khat (Catha edulis) East Afr Med J. 2000;77:329–332. - PubMed
- Magdum SS. An Overview of Khat. Addict Disord Treat. 2011;10:72–83.
- U.S. Department of Justice, Drug Enforcement Administration. Synthetic Cathinones - DEA Request for Information. Washington, DC: 2011. pp. 1–2.
- Drug Enforcement Administration. Background, data and analysis of synthetic cathinones: Mephedrone (4-MMC), methylone (MDMC) and 3,4-methylenedioxypyrovalerone (MDPV) Washington, DC: U.S Department of Justice, Office of Diversion Control Drug and Chemical Evaluation Section; 2011. pp. 1–29.
LinkOut - more resources
Full Text Sources
Other Literature Sources