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Reinforcing Effects of Cathinone NPS in the Intravenous Drug Self-Administration Paradigm

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Neuropharmacology of New Psychoactive Substances (NPS)

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 32))

Abstract

Since the mid- to late 2000s, there has been a dramatic rise in the use and abuse of synthetic derivatives of cathinone, a stimulant alkaloid found in the African shrub Catha edulis. Cathinone novel psychoactive substances (NPS), also referred to as synthetic cathinones or “bath salt”-type drugs, have gained popularity among drug users due to their potency, low cost, ease of procurement, and diverse array of evolving chemical structures. While the ability of cathinone NPS to produce psychotomimetic effects, multiple organ system toxicity, and death in humans is well documented, there has been limited scientific investigation into the reinforcing effects and abuse liability of these drugs. In this chapter, we will summarize the existing literature on the reinforcing effects of cathinone NPS in rodents using the intravenous self-administration (IVSA) paradigm. We will also compare the ability of cathinone NPS to serve as reinforcers to that of classical psychostimulants such as cocaine, methamphetamine, and methylenedioxymethamphetamine (MDMA). The chapter will conclude with a summary and indications for future avenues of research on cathinone NPS.

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References

  1. Association of Poison Control Centers (2013) Bath salts data. 30 April 2013

    Google Scholar 

  2. Baumeister D, Tojo LM, Tracy DK (2015) Legal highs: staying on top of the flood of novel psychoactive substances. Ther Adv Psychopharmacol 5:97–132

    PubMed  PubMed Central  Google Scholar 

  3. Karch SB (2015) Cathinone neurotoxicity (“the 3Ms”). Curr Neuropharmacol 13:21–25

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Underwood E (2015) A new drug war. Science 347:469–473

    CAS  PubMed  Google Scholar 

  5. Weaver MF, Hopper JA, Gunderson EW (2015) Designer drugs 2015: assessment and management. Addict Sci Clin Pract 10:8

    PubMed  PubMed Central  Google Scholar 

  6. Zawilska JB (2015) “Legal highs” - an emerging epidemic of novel psychoactive substances. Int Rev Neurobiol 120:273–300

    CAS  PubMed  Google Scholar 

  7. Banks ML, Worst TJ, Rusyniak DE, Sprague JE (2014) Synthetic cathinones (“bath salts”). J Emerg Med 46:632–642

    PubMed  PubMed Central  Google Scholar 

  8. Froberg BA, Levine M, Beuhler MC, Judge BS, Moore PW, Engebretsen KM, McKeown NJ, Rosenbaum CD, Young AC, Rusyniak DE (2015) Acute methylenedioxypyrovalerone toxicity. J Med Toxicol 11:185–194

    CAS  PubMed  Google Scholar 

  9. Hall C, Heyd C, Butler C, Yarema M (2014) “Bath salts” intoxication: a new recreational drug that presents with a familiar toxidrome. CJEM 16:171–176

    PubMed  Google Scholar 

  10. Karila L, Megarbane B, Cottencin O, Lejoyeux M (2015) Synthetic cathinones: a new public health problem. Curr Neuropharmacol 13:12–20

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Batisse A, Fortias M, Bourgogne E, Gregoire M, Sec I, Djezzar S (2014) Case series of 21 synthetic cathinones abuse. J Clin Psychopharmacol 34:411–413

    PubMed  Google Scholar 

  12. Baumann MH (2014) Awash in a sea of ‘bath salts’: implications for biomedical research and public health. Addiction 109:1577–1579

    PubMed  PubMed Central  Google Scholar 

  13. Capriola M (2013) Synthetic cathinone abuse. Clin Pharmacol Adv Appl 5:109–115

    Google Scholar 

  14. Fass JA, Fass AD, Garcia AS (2012) Synthetic cathinones (bath salts): legal status and patterns of abuse. Ann Pharmacother 46:436–441

    PubMed  Google Scholar 

  15. Paillet-Loilier M, Cesbron A, Le Boisselier R, Bourgine J, Debruyne D (2014) Emerging drugs of abuse: current perspectives on substituted cathinones. Subst Abuse Rehabil 5:37–52

    PubMed  PubMed Central  Google Scholar 

  16. Sadeg N, Darie A, Vilamot B, Passamar M, Frances B, Belhadj-Tahar H (2014) Case report of cathinone-like designer drug intoxication psychosis and addiction with serum identification. Addict Disord Treat 13:38–43

    Google Scholar 

  17. Winder GS, Stern N, Hosanagar A (2013) Are “bath salts” the next generation of stimulant abuse? J Subst Abuse Treat 44:42–45

    PubMed  Google Scholar 

  18. Watterson LR, Olive MF (2014) Synthetic cathinones and their rewarding and reinforcing effects in rodents. Adv Neurosci 2014:209875

    Google Scholar 

  19. Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW (2013) Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive ‘bath salts’ products. Neuropsychopharmacology 38:552–562

    CAS  PubMed  Google Scholar 

  20. Cameron K, Kolanos R, Verkariya R, De Felice L, Glennon RA (2013) Mephedrone and methylenedioxypyrovalerone (MDPV), major constituents of “bath salts,” produce opposite effects at the human dopamine transporter. Psychopharmacology (Berl) 227:493–499

    CAS  PubMed  Google Scholar 

  21. Cameron KN, Kolanos R, Solis E, Glennon RA, De Felice LJ (2013) Bath salts components mephedrone and methylenedioxypyrovalerone (MDPV) act synergistically at the human dopamine transporter. Br J Pharmacol 168:1750–1757

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Coppola M, Mondola R (2012) 3,4-methylenedioxypyrovalerone (MDPV): chemistry, pharmacology and toxicology of a new designer drug of abuse marketed online. Toxicol Lett 208:12–15

    CAS  PubMed  Google Scholar 

  23. De Felice LJ, Glennon RA, Negus SS (2014) Synthetic cathinones: chemical phylogeny, physiology, and neuropharmacology. Life Sci 97:20–26

    PubMed  Google Scholar 

  24. Glennon RA (2014) Bath salts, mephedrone, and methylenedioxypyrovalerone as emerging illicit drugs that will need targeted therapeutic intervention. Adv Pharmacol 69:581–620

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Kolanos R, Partilla JS, Baumann MH, Hutsell BA, Banks ML, Negus SS, Glennon RA (2015) Stereoselective actions of methylenedioxypyrovalerone (MDPV) to inhibit dopamine and norepinephrine transporters and facilitate intracranial self-stimulation in rats. ACS Chem Neurosci 6:771–777

    CAS  PubMed  Google Scholar 

  26. Kolanos R, Solis EJ, Sakloth F, De Felice LJ, Glennon RA (2013) “Deconstruction” of the abused synthetic cathinone methylenedioxypyrovalerone (MDPV) and an examination of effects at the human dopamine transporter. ACS Chem Neurosci 4:1524–1529

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Simmler L, Buser T, Donzelli M, Schramm Y, Dieu LH, Huwyler J, Chaboz S, Hoener M, Liechti M (2013) Pharmacological characterization of designer cathinones in vitro. J Comp Neurol 168:458–470

    CAS  Google Scholar 

  28. Baumann MH, Ayestas MA Jr, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV (2012) The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacology 37:1192–1203

    CAS  PubMed  Google Scholar 

  29. Eshleman AJ, Wolfrum KM, Hatfield MG, Johnson RA, Murphy KV, Janowsky A (2013) Substituted methcathinones differ in transporter and receptor interactions. Biochem Pharmacol 85:1803–1815

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Lopez-Arnau R, Martinez-Clemente J, Carbo M, Pubill D, Escubedo E, Camarasa J (2013) An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as “bath salts”. Prog Neuropsychopharmacol Biol Psychiatry 45:64–72

    CAS  PubMed  Google Scholar 

  31. Cozzi NV, Sievert MK, Shulgin AT, Jacob P III, Ruoho AE (1999) Inhibition of plasma membrane monoamine transporters by Beta-keto amphetamines. Eur J Pharmacol 381:63–69

    CAS  PubMed  Google Scholar 

  32. Pifl C, Reither H, Hornykiewicz O (2015) The profile of mephedrone on human monoamine transporters differs from 3,4-methylenedioxymethamphetamine primarily by lower potency at the vesicular monoamine transporter. Eur J Pharmacol 755:119–126

    CAS  PubMed  Google Scholar 

  33. Gosnell BA, Yracheta JM, Bell SM, Lane KE (1996) Intravenous self-administration of cathinone by rats. Behav Pharmacol 7:526–531

    CAS  PubMed  Google Scholar 

  34. Kaminski BJ, Griffiths RR (1994) Intravenous self-injection of methcathinone in the baboon. Pharmacol Biochem Behav 47:981–983

    CAS  PubMed  Google Scholar 

  35. Woolverton WL, Johanson CE (1984) Preference in rhesus monkeys given a choice between cocaine and d, l-cathinone. J Exp Anal Behav 41:35–43

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Watterson LR, Watterson E, Olive MF (2013) Abuse liability of novel ‘legal high’ designer stimulants: evidence from animal models. Behav Pharmacol 24:341–355

    PubMed  PubMed Central  Google Scholar 

  37. Hadlock GC, Webb KM, McFadden LM, Chu PW, Ellis JD, Allen SC, Andrenyak DM, Vieira-Brock PL, German CL, Conrad KM, Hoonakker AJ, Gibb JW, Wilkins DG, Hanson GR, Fleckenstein AE (2011) 4-Methylmethcathinone (mephedrone): neuropharmacological effects of a designer stimulant of abuse. J Pharmacol Exp Ther 339:530–536

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Aarde SM, Angrish D, Barlow DJ, Wright MJJ, Vandewater SA, Creehan KM, Houseknecht KL, Dickerson TJ, Taffe MA (2013) Mephedrone (4-methylmethcathinone) supports intravenous self-administration in Sprague-Dawley and Wistar rats. Addict Biol 18:768–799

    Google Scholar 

  39. Kitamura O, Wee S, Specio SE, Koob GF, Pulvirenti L (2006) Escalation of methamphetamine self-administration in rats: a dose-effect function. Psychopharmacology (Berl) 186:48–53

    CAS  PubMed  Google Scholar 

  40. Motbey CP, Clemens KJ, Apetz N, Winstock AR, Ramsey J, Li KM, Wyatt N, Callaghan PD, Bowen MT, Cornish JL, McGregor IS (2013) High levels of intravenous mephedrone (4-methylmethcathinone) self-administration in rats: Neural consequences and comparison with methamphetamine. J Psychopharmacol 27:823–836

    CAS  PubMed  Google Scholar 

  41. Creehan KM, Vandewater SA, Taffe MA (2015) Intravenous self-administration of mephedrone, methylone and MDMA in female rats. Neuropharmacology 92:90–97

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Vandewater SA, Creehan KM, Taffe MA (2015) Intravenous self-administration of entactogen-class stimulants in male rats. Neuropharmacology 99:538–545

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Aarde SM, Huang PK, Creehan KM, Dickerson TJ, Taffe MA (2013) The novel recreational drug 3,4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: self-administration and locomotor activity in rats. Neuropharmacology 71:130–140

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Aarde SM, Huang PK, Dickerson TJ, Taffe MA (2015) Binge-like acquisition of 3,4-methylenedioxypyrovalerone (MDPV) self-administration and wheel activity in rats. Psychopharmacology (Berl) 232:1867–1877

    CAS  PubMed  Google Scholar 

  45. Watterson LR, Kufahl PR, Nemirovsky NE, Sewalia K, Grabenauer M, Thomas BF, Marusich JA, Wegner S, Olive MF (2014) Potent rewarding and reinforcing effects of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV). Addict Biol 19:165–174

    CAS  PubMed  Google Scholar 

  46. Schindler CW, Thorndike EB, Goldberg SR, Lehner KR, Cozzi NV, Brandt SD, Baumann MH (2016) Reinforcing and neurochemical effects of the “bath salts” constituents 3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) in male rats. Psychopharmacology (Berl) 233:1981–1990

    CAS  PubMed  Google Scholar 

  47. Watterson LR, Hood LE, Sewalia K, Johnson CT, Wegner S, Grabenauer M, Thomas BF, Marusich JA, Olive MF (2012) The reinforcing effects of the methylone, a synthetic cathinone commonly found in “bath salts”. J Addict Res Ther S9:002

    Google Scholar 

  48. Watterson LR, Burrows BT, Hernandez RD, Moore KN, Grabenauer M, Marusich JA, Olive MF (2014) 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. Int J Neuropsychopharmacol 18:1–9

    Google Scholar 

  49. Aarde SM, Creehan KM, Vandewater SA, Dickerson TJ, Taffe MA (2015) In vivo potency and efficacy of the novel cathinone α-pyrrolidinopentiophenone and 3,4-methylenedioxypyrovalerone: self-administration and locomotor stimulation in male rats. Psychopharmacology (Berl) 232:3045–3055

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Marusich JA, Antonazzo KR, Wiley JL, Blough BE, Partilla JS, Baumann MH (2014) Pharmacology of novel synthetic stimulants structurally related to the “bath salts” constituent 3,4-methylenedioxypyrovalerone (MDPV). Neuropharmacology 87:206–213

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Roberts DCS, Phelan R, Hodges LM, Hodges MM, Bennett B, Childers S, Davies H (1999) Self-administration of cocaine analogs by rats. Psychopharmacology (Berl) 144:389–397

    CAS  PubMed  Google Scholar 

  52. Wee S, Anderson KG, Baumann MH, Rothman RB, Blough BE, Woolverton WL (2005) Relationship between the serotonergic activity and reinforcing effects of a series of amphetamine analogs. J Pharmacol Exp Ther 313:848–854

    CAS  PubMed  Google Scholar 

  53. Wee S, Carroll FI, Woolverton WL (2006) A reduced rate of in vivo dopamine transporter binding is associated with lower relative reinforcing efficacy of stimulants. Neuropsychopharmacology 31:351–362

    CAS  PubMed  Google Scholar 

  54. Gass JT, Olive MF (2008) Glutamatergic substrates of drug addiction and alcoholism. Biochem Pharmacol 75:218–265

    CAS  PubMed  Google Scholar 

  55. Liberles SD (2015) Trace amine-associated receptors: ligands, neural circuits, and behaviors. Curr Opin Neurobiol 34:1–7

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors wish to acknowledge Public Health Service grant R01DA025606 from the National Institute on Drug Abuse for supporting our initial studies on cathinone NPS abuse potential.

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Authors and Affiliations

  1. Department of Psychology, Arizona State University, 871104, Tempe, AZ, 85287, USA

    Lucas R. Watterson & M. Foster Olive

Authors
  1. Lucas R. Watterson
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  2. M. Foster Olive
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Correspondence to M. Foster Olive .

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Editors and Affiliations

  1. Designer Drug Research Unit (DDRU), National Institute on Drug Abuse, Baltimore, MD, USA

    Michael H. Baumann

  2. Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, USA

    Richard A. Glennon

  3. RTI International, Research Triangle Park, NC, USA

    Jenny L. Wiley

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Watterson, L.R., Olive, M.F. (2016). Reinforcing Effects of Cathinone NPS in the Intravenous Drug Self-Administration Paradigm. In: Baumann, M.H., Glennon, R.A., Wiley, J.L. (eds) Neuropharmacology of New Psychoactive Substances (NPS). Current Topics in Behavioral Neurosciences, vol 32. Springer, Cham. https://doi.org/10.1007/7854_2016_33

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