Abstract
Animal models of drug self-administration are currently the gold standard for making predictions regarding the relative likelihood that a recreational drug substance will lead to continued use and addiction. Such models have been found to have high predictive accuracy and discriminative validity for a number of drug classes including ethanol, nicotine, opioids, and psychostimulants such as cocaine and methamphetamine. Members of the entactogen class of psychostimulants (drugs that produce an “open mind state” including feelings of interpersonal closeness, intimacy and empathy) have been less frequently studied in self-administration models. The prototypical entactogen 3,4-methylenedioxymethamphetamine (MDMA; “Ecstasy”) supports self-administration but not with the same consistency nor with the same efficacy as structurally related drugs amphetamine or methamphetamine. Consistent with these observations, MDMA use is more episodic in the majority of those who use it frequently. Nevertheless, substantial numbers of MDMA users will meet the criteria for substance dependence at some point in their use history. This review examines the currently available evidence from rodent self-administration studies of MDMA and two of the new and emerging psychoactive substances (NPS) that produce entactogen type neuropharmacological responses – mephedrone (4-methylmethcathinone; 4MMC; “meow meow”) and methylone (3,4-methylenedioxymethcathinone). Overall, the current evidence predicts that these NPS entactogens have enhanced abuse liability compared with MDMA.
References
Wikipedia (2015) Empathogen-entactogen 2015 [cited]. https://en.wikipedia.org/wiki/Empathogen-entactogen
Nichols DE (1986) Differences between the mechanism of action of MDMA, MBDB, and the classic hallucinogens. Identification of a new therapeutic class: entactogens. J Psychoactive Drugs 18:305–313
EcstasyData.org (2006) EcstasyData.org: ecstasy lab testing and analysis results – ecstasy pill reports 2006 [cited]. www.ecstasydata.org
Johnston LD, O’Malley PM, Bachman JG, Scheulenberg JE, Miech RA (2015) Monitoring the future national survey results on drug use, 1975-2014. Volume I, Secondary school students. University of Michigan, Ann Arbor, p. 599
Johnston LD, O’Malley PM, Bachman JG, Schulenberg JE, Miech RA (2015) Monitoring the future national survey results on drug use, 1975-2014. Volume II, College students and adults ages 19-55. University of Michigan, Ann Arbor, p. 439
Doblin R (2006) MAPS-sponsored cancer anxiety research. MAPS Bull 16:11
Mithoefer M (2006) MDMA-assisted psychotherapy in the treatment of posttraumatic stress disorder (PTSD): seventh update on study progress. MAPS Bull 16:7–8
Mojeiko V (2006) Israel MDMA/PTSD research project. MAPS Bull 16:10
Oehen P (2006) MDMA-assisted psychotherapy pilot study in Switzerland. MAPS Bull 16:9
Amoroso T (2015) The psychopharmacology of +/-3,4 methylenedioxymethamphetamine and its role in the treatment of posttraumatic stress disorder. J Psychoactive Drugs:1–8
Parrott AC (2014) The potential dangers of using MDMA for psychotherapy. J Psychoactive Drugs 46:37–43
White CM (2014) 3,4-Methylenedioxymethamphetamine’s (MDMA’s) Impact on Posttraumatic Stress Disorder. Ann Pharmacother 48:908–915
Greer G, Tolbert R (1986) Subjective reports of the effects of MDMA in a clinical setting. J Psychoactive Drugs 18:319–327
Parrott AC (2005) Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or ecstasy. J Psychopharmacol 19:71–83
von Sydow K, Lieb R, Pfister H, Hofler M, Wittchen HU (2002) Use, abuse and dependence of ecstasy and related drugs in adolescents and young adults-a transient phenomenon? Results from a longitudinal community study. Drug Alcohol Depend 66:147–159
Cottler LB, Womack SB, Compton WM, Ben-Abdallah A (2001) Ecstasy abuse and dependence among adolescents and young adults: applicability and reliability of DSM-IV criteria. Hum Psychopharmacol 16:599–606
Schuster P, Lieb R, Lamertz C, Wittchen HU (1998) Is the use of ecstasy and hallucinogens increasing? Results from a community study. Eur Addict Res 4:75–82
Thomasius R, Petersen KU, Zapletalova P, Wartberg L, Zeichner D, Schmoldt A (2005) Mental disorders in current and former heavy ecstasy (MDMA) users. Addiction 100:1310–1319
Hurault de Ligny B, El Haggan W, Comoz F, Lobbedez T, Pujo M, Griveau AM, Bottet P, Bensadoun H, Ryckelynck JP (2005) Early loss of two renal grafts obtained from the same donor: role of ecstasy? Transplantation 80:153–156
Jansen KL (1999) Ecstasy (MDMA) dependence. Drug Alcohol Depend 53:121–124
Kouimtsidis C, Schifano F, Sharp T, Ford L, Robinson J, Magee C (2006) Neurological and psychopathological sequelae associated with a lifetime intake of 40,000 ecstasy tablets. Psychosomatics 47:86–87
Fox HC, Parrott AC, Turner JJ (2001) Ecstasy use: cognitive deficits related to dosage rather than self-reported problematic use of the drug. J Psychopharmacol 15:273–281
Hanson KL, Luciana M (2004) Neurocognitive function in users of MDMA: the importance of clinically significant patterns of use. Psychol Med 34:229–246
MacInnes N, Handley SL, Harding GF (2001) Former chronic methylenedioxymethamphetamine (MDMA or ecstasy) users report mild depressive symptoms. J Psychopharmacol 15:181–186
Morgan MJ (1999) Memory deficits associated with recreational use of “ecstasy” (MDMA). Psychopharmacology (Berl) 141:30–36
Quednow BB, Kuhn KU, Hoppe C, Westheide J, Maier W, Daum I, Wagner M (2007) Elevated impulsivity and impaired decision-making cognition in heavy users of MDMA (“Ecstasy”). Psychopharmacology (Berl) 189:517–530
Ward J, Hall K, Haslam C (2006) Patterns of memory dysfunction in current and 2-year abstinent MDMA users. J Clin Exp Neuropsychol 28:306–324
White B, Day C, Degenhardt L, Kinner S, Fry C, Bruno R, Johnston J (2006) Prevalence of injecting drug use and associated risk behavior among regular ecstasy users in Australia. Drug Alcohol Depend 83:210–217
Johanson CE, Frey KA, Lundahl LH, Keenan P, Lockhart N, Roll J, Galloway GP, Koeppe RA, Kilbourn MR, Robbins T, Schuster CR (2006) Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers. Psychopharmacology (Berl) 185:327–338
Johnson BA, Roache JD, Ait-Daoud N, Wells LT, Wallace CL, Dawes MA, Liu L, Wang XQ (2007) Effects of topiramate on methamphetamine-induced changes in attentional and perceptual-motor skills of cognition in recently abstinent methamphetamine-dependent individuals. Prog Neuropsychopharmacol Biol Psychiatry 31:123–130
Rippeth JD, Heaton RK, Carey CL, Marcotte TD, Moore DJ, Gonzalez R, Wolfson T, Grant I (2004) Methamphetamine dependence increases risk of neuropsychological impairment in HIV infected persons. J Int Neuropsychol Soc 10:1–14
Gouzoulis-Mayfrank E, Daumann J (2006) The confounding problem of polydrug use in recreational ecstasy/MDMA users: a brief overview. J Psychopharmacol 20:188–193
Wish ED, Fitzelle DB, O’Grady KE, Hsu MH, Arria AM (2006) Evidence for significant polydrug use among ecstasy-using college students. J Am Coll Health 55:99–104
Wu LT, Ringwalt CL, Weiss RD, Blazer DG (2009) Hallucinogen-related disorders in a national sample of adolescents: the influence of ecstasy/MDMA use. Drug Alcohol Depend 104:156–166
Cottler LB, Leung KS, Abdallah AB (2009) Test-re-test reliability of DSM-IV adopted criteria for 3,4-methylenedioxymethamphetamine (MDMA) abuse and dependence: a cross-national study. Addiction 104:1679–1690
Degenhardt L, Bruno R, Topp L (2009) Is ecstasy a drug of dependence? Drug Alcohol Depend 107:1–10
Winstock A, Mitcheson L, Ramsey J, Davies S, Puchnarewicz M, Marsden J (2011) Mephedrone: use, subjective effects and health risks. Addiction 106:1991–1996
Winstock AR, Mitcheson LR, Deluca P, Davey Z, Corazza O, Schifano F (2011) Mephedrone, new kid for the chop? Addiction 106:154–161
Winstock A, Mitcheson L, Marsden J (2010) Mephedrone: still available and twice the price. Lancet 376:1537–1537
Brunt TM, Niesink RJ, van den Brink W (2012) Impact of a transient instability of the ecstasy market on health concerns and drug use patterns in The Netherlands. Int J Drug Policy 23:134–140
Brunt TM, Poortman A, Niesink RJ, van den Brink W (2011) Instability of the ecstasy market and a new kid on the block: mephedrone. J Psychopharmacol 25(11):1543–1547
DEA (2011) Schedules of controlled substances: temporary placement of three synthetic cathinones in Schedule I. Final order. Fed Regist 76:65371–65375
Moore K, Dargan PI, Wood DM, Measham F (2013) Do novel psychoactive substances displace established club drugs, supplement them or act as drugs of initiation? The relationship between mephedrone, ecstasy and cocaine. Eur Addict Res 19:276–282
Leung KS, Ben Abdallah A, Copeland J, Cottler LB (2010) Modifiable risk factors of ecstasy use: risk perception, current dependence, perceived control, and depression. Addict Behav 35:201–208
Ding Y, He N, Shoptaw S, Gao M, Detels R (2014) Severity of club drug dependence and perceived need for treatment among a sample of adult club drug users in Shanghai, China. Soc Psychiatry Psychiatr Epidemiol 49:395–404
Uosukainen H, Tacke U, Winstock AR (2015) Self-reported prevalence of dependence of MDMA compared to cocaine, mephedrone and ketamine among a sample of recreational poly-drug users. Int J Drug Policy 26:78–83
DEA (2014) National Forensic Laboratory Information System: midyear report 2013. U.S. Drug Enforcement Administration, Springfield, VA
DEA (2015) National Forensic Laboratory Information System: midyear report 2014. U.S. Drug Enforcement Administration, Springfield, VA
Lusthof KJ, Oosting R, Maes A, Verschraagen M, Dijkhuizen A, Sprong AG (2011) A case of extreme agitation and death after the use of mephedrone in The Netherlands. Forensic Sci Int 206:e93–e95
Patel MM, Wright DW, Ratcliff JJ, Miller MA (2004) Shedding new light on the “safe” club drug: methylenedioxymethamphetamine (ecstasy)-related fatalities. Acad Emerg Med 11:208–210
Pearson JM, Hargraves TL, Hair LS, Massucci CJ, Frazee CC, Garg U, Pietak BR (2012) Three fatal intoxications due to methylone. J Anal Toxicol 36:444–451
Schifano F (2004) A bitter pill. Overview of ecstasy (MDMA, MDA) related fatalities. Psychopharmacology (Berl) 173:242–248
Torrance H, Cooper G (2010) The detection of mephedrone (4-methylmethcathinone) in 4 fatalities in Scotland. Forensic Sci Int 202:e62–e63
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
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
Lopez-Arnau R, Martinez-Clemente J, Pubill D, Escubedo E, Camarasa J (2012) Comparative neuropharmacology of three psychostimulant cathinone derivatives: butylone, mephedrone and methylone. Br J Pharmacol 167:407–420
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. Br J Pharmacol 168:458–470
Simmler LD, Rickli A, Hoener MC, Liechti ME (2014) Monoamine transporter and receptor interaction profiles of a new series of designer cathinones. Neuropharmacology 79:152–160
Kehr J, Ichinose F, Yoshitake S, Goiny M, Sievertsson T, Nyberg F, Yoshitake T (2011) Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats. Br J Pharmacol 164:1949–1958
Wright MJ Jr, Angrish D, Aarde SM, Barlow DJ, Buczynski MW, Creehan KM, Vandewater SA, Parsons LH, Houseknecht KL, Dickerson TJ, Taffe MA (2012) Effect of ambient temperature on the thermoregulatory and locomotor stimulant effects of 4-methylmethcathinone in Wistar and Sprague-Dawley rats. PLoS One 7:e44652
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
Negus SS, Mello NK, Blough BE, Baumann MH, Rothman RB (2007) Monoamine releasers with varying selectivity for dopamine/norepinephrine vs. serotonin release as candidate “agonist” medications for cocaine dependence: studies in assays of cocaine discrimination and cocaine self-administration in rhesus monkeys. J Pharmacol Exp Ther 320:627–636
Roberts DC, 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
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
Howell LL, Carroll FI, Votaw JR, Goodman MM, Kimmel HL (2007) Effects of combined dopamine and serotonin transporter inhibitors on cocaine self-administration in rhesus monkeys. J Pharmacol Exp Ther 320(2):757–765
Wee S, Woolverton WL (2006) Self-administration of mixtures of fenfluramine and amphetamine by rhesus monkeys. Pharmacol Biochem Behav 84:337–343
Fletcher PJ, Robinson SR, Slippoy DL (2001) Pre-exposure to (+/-)3,4-methylenedioxy-methamphetamine (MDMA) facilitates acquisition of intravenous cocaine self-administration in rats. Neuropsychopharmacology 25:195–203
Morley KC, Cornish JL, Li KM, McGregor IS (2004) Preexposure to MDMA (“Ecstasy”) delays acquisition but facilitates MDMA-induced reinstatement of amphetamine self-administration behavior in rats. Pharmacol Biochem Behav 79:331–342
Bradbury S, Bird J, Colussi-Mas J, Mueller M, Ricaurte G, Schenk S (2014) Acquisition of MDMA self-administration: pharmacokinetic factors and MDMA-induced serotonin release. Addict Biol 19:874–884
Oakly AC, Brox BW, Schenk S, Ellenbroek BA (2014) A genetic deletion of the serotonin transporter greatly enhances the reinforcing properties of MDMA in rats. Mol Psychiatry 19:534–535
O’Connor EC, Chapman K, Butler P, Mead AN (2011) The predictive validity of the rat self-administration model for abuse liability. Neurosci Biobehav Rev 35:912–938
Wise RA, Koob GF (2014) The development and maintenance of drug addiction. Neuropsychopharmacology 39:254–262
Robinson TE (2004) Neuroscience. Addicted rats. Science 305:951–953
Gardner EL (2000) What we have learned about addiction from animal models of drug self-administration. Am J Addict 9:285–313
Panlilio LV, Goldberg SR (2007) Self-administration of drugs in animals and humans as a model and an investigative tool. Addiction 102:1863–1870
Schenk S, Gittings D, Johnstone M, Daniela E (2003) Development, maintenance and temporal pattern of self-administration maintained by ecstasy (MDMA) in rats. Psychopharmacology (Berl) 169:21–27
Schenk S, Hely L, Lake B, Daniela E, Gittings D, Mash DC (2007) MDMA self-administration in rats: acquisition, progressive ratio responding and serotonin transporter binding. Eur J Neurosci 26:3229–3236
Ahmed SH (2010) Validation crisis in animal models of drug addiction: beyond non-disordered drug use toward drug addiction. Neurosci Biobehav Rev 35:172–184
Hodos W (1961) Progressive ratio as a measure of reward strength. Science (New York, NY) 134:943–944
Hodos W, Kalman G (1963) Effects of increment size and reinforcer volume on progressive ratio performance. J Exp Anal Behav 6:387–392
Richardson NR, Roberts DC (1996) Progressive ratio schedules in drug self-administration studies in rats: a method to evaluate reinforcing efficacy. J Neurosci Methods 66:1–11
Oleson EB, Richardson JM, Roberts DC (2011) A novel IV cocaine self-administration procedure in rats: differential effects of dopamine, serotonin, and GABA drug pre-treatments on cocaine consumption and maximal price paid. Psychopharmacology (Berl) 214:567–577
Bradshaw CM, Killeen PR (2012) A theory of behaviour on progressive ratio schedules, with applications in behavioural pharmacology. Psychopharmacology (Berl) 222:549–564
Killeen PR, Sanabria F, Dolgov I (2009) The dynamics of conditioning and extinction. J Exp Psychol Anim Behav Process 35:447–472
Ahmed SH, Koob GF (1999) Long-lasting increase in the set point for cocaine self-administration after escalation in rats. Psychopharmacology (Berl) 146:303–312
Anker JJ, Baron TR, Zlebnik NE, Carroll ME (2012) Escalation of methamphetamine self-administration in adolescent and adult rats. Drug Alcohol Depend 124:149–153
Edwards S, Koob GF (2013) Escalation of drug self-administration as a hallmark of persistent addiction liability. Behav Pharmacol 24:356–362
Deroche-Gamonet V, Belin D, Piazza PV (2004) Evidence for addiction-like behavior in the rat. Science 305:1014–1017
Kearns DN, Weiss SJ, Panlilio LV (2002) Conditioned suppression of behavior maintained by cocaine self-administration. Drug Alcohol Depend 65:253–261
Vanderschuren LJ, Everitt BJ (2004) Drug seeking becomes compulsive after prolonged cocaine self-administration. Science 305:1017–1019
Gancarz-Kausch AM, Adank DN, Dietz DM (2014) Prolonged withdrawal following cocaine self-administration increases resistance to punishment in a cocaine binge. Sci Rep 4:6876
Holtz NA, Carroll ME (2015) Cocaine self-administration punished by intravenous histamine in adolescent and adult rats. Behav Pharmacol 26:393–397
Woolverton WL, Freeman KB, Myerson J, Green L (2012) Suppression of cocaine self-administration in monkeys: effects of delayed punishment. Psychopharmacology (Berl) 220:509–517
Comer SD, Lac ST, Curtis LK, Carroll ME (1993) Effects of buprenorphine and naltrexone on reinstatement of cocaine-reinforced responding in rats. J Pharmacol Exp Ther 267:1470–1477
Lenoir M, Ahmed SH (2007) Heroin-induced reinstatement is specific to compulsive heroin use and dissociable from heroin reward and sensitization. Neuropsychopharmacology 32:616–624
Lynch WJ, Carroll ME (2000) Reinstatement of cocaine self-administration in rats: sex differences. Psychopharmacology (Berl) 148:196–200
Martin-Fardon R, Maurice T, Aujla H, Bowen WD, Weiss F (2007) Differential effects of sigma1 receptor blockade on self-administration and conditioned reinstatement motivated by cocaine vs natural reward. Neuropsychopharmacology 32:1967–1973
Ahmed SH, Lenoir M, Guillem K (2013) Neurobiology of addiction versus drug use driven by lack of choice. Curr Opin Neurobiol 23:581–587
Cosgrove KP, Hunter RG, Carroll ME (2002) Wheel-running attenuates intravenous cocaine self-administration in rats: sex differences. Pharmacol Biochem Behav 73:663–671
Miller ML, Vaillancourt BD, Wright MJ Jr, Aarde SM, Vandewater SA, Creehan KM, Taffe MA (2012) Reciprocal inhibitory effects of intravenous d-methamphetamine self-administration and wheel activity in rats. Drug Alcohol Depend 121:90–96
Aarde SM, Angrish D, Barlow DJ, Wright MJ Jr, 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 18:786–799
Dalley JW, Lääne K, Theobald DEH, Peña Y, Bruce CC, Huszar AC, Wojcieszek M, Everitt BJ, Robbins TW (2007) Enduring deficits in sustained visual attention during withdrawal of intravenous methylenedioxymethamphetamine self-administration in rats: results from a comparative study with d-amphetamine and methamphetamine. Neuropsychopharmacology 32:1195–1206
Miller ML, Aarde SM, Moreno AY, Creehan KM, Janda KD, Taffe MA (2015) Effects of active anti-methamphetamine vaccination on intravenous self-administration in rats. Drug Alcohol Depend 153:29–36
Ranaldi R, Poeggel K (2002) Baclofen decreases methamphetamine self-administration in rats. Neuroreport 13:1107–1110
Yokel RA, Pickens R (1973) Self-administration of optical isomers of amphetamine and methylamphetamine by rats. J Pharmacol Exp Ther 187:27–33
Balster RL, Schuster CR (1973) A comparison of d-amphetamine, l-amphetamine, and methamphetamine self-administration in rhesus monkeys. Pharmacol Biochem Behav 1:67–71
Beardsley PM, Balster RL, Harris LS (1986) Self-administration of methylenedioxymethamphetamine (MDMA) by rhesus monkeys. Drug Alcohol Depend 18:149–157
Kangas BD, Bergman J (2015) Effects of self-administered methamphetamine on discrimination learning and reversal in nonhuman primates. Psychopharmacology (Berl) 233:373–380
Newman JL, Carroll ME (2006) Reinforcing effects of smoked methamphetamine in rhesus monkeys. Psychopharmacology (Berl) 188:193–200
Yasar S, Gaal J, Panlilio LV, Justinova Z, Molnar SV, Redhi GH, Schindler CW (2006) A comparison of drug-seeking behavior maintained by D-amphetamine, L-deprenyl (selegiline), and D-deprenyl under a second-order schedule in squirrel monkeys. Psychopharmacology (Berl) 183:413–421
Balster RL, Kilbey MM, Ellinwood EH Jr (1976) Methamphetamine self-administration in the cat. Psychopharmacologia 46:229–233
Griffiths RR, Winger G, Brady JV, Snell JD (1976) Comparison of behavior maintained by infusions of eight phenylethylamines in baboons. Psychopharmacology (Berl) 50:251–258
Fantegrossi WE, Ullrich T, Rice KC, Woods JH, Winger G (2002) 3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) and its stereoisomers as reinforcers in rhesus monkeys: serotonergic involvement. Psychopharmacology (Berl) 161:356–364
Fantegrossi WE, Woolverton WL, Kilbourn M, Sherman P, Yuan J, Hatzidimitriou G, Ricaurte GA, Woods JH, Winger G (2004) Behavioral and neurochemical consequences of long-term intravenous self-administration of MDMA and its enantiomers by rhesus monkeys. Neuropsychopharmacology 29:1270–1281
Lamb RJ, Griffiths RR (1987) Self-injection of d,1-3,4-methylenedioxymethamphetamine (MDMA) in the baboon. Psychopharmacology (Berl) 91:268–272
Lile JA, Ross JT, Nader MA (2005) A comparison of the reinforcing efficacy of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) with cocaine in rhesus monkeys. Drug Alcohol Depend 78:135–140
Markert LE, Roberts DC (1991) 3,4-Methylenedioxyamphetamine (MDA) self-administration and neurotoxicity. Pharmacol Biochem Behav 39:569–574
Ball KT, Jarsocrak H, Hyacinthe J, Lambert J, Lockowitz J, Schrock J (2015) Yohimbine reinstates extinguished 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) seeking in rats with prior exposure to chronic yohimbine. Behav Brain Res 294:1–6
Ball KT, Walsh KM, Rebec GV (2007) Reinstatement of MDMA (ecstasy) seeking by exposure to discrete drug-conditioned cues. Pharmacol Biochem Behav 87:420–425
Creehan KM, Vandewater SA, Taffe MA (2015) Intravenous self-administration of mephedrone, methylone and MDMA in female rats. Neuropharmacology 92:90–97
De La Garza R 2nd, Fabrizio KR, Gupta A (2007) Relevance of rodent models of intravenous MDMA self-administration to human MDMA consumption patterns. Psychopharmacology (Berl) 189:425–434
Ratzenboeck E, Saria A, Kriechbaum N, Zernig G (2001) Reinforcing effects of MDMA (“ecstasy”) in drug-naive and cocaine-trained rats. Pharmacology 62:138–144
Vandewater SA, Creehan KM, Taffe MA (2015) Intravenous self-administration of entactogen-class stimulants in male rats. Neuropharmacology 99:538–545
Daniela E, Brennan K, Gittings D, Hely L, Schenk S (2004) Effect of SCH 23390 on (+/-)-3,4-methylenedioxymethamphetamine hyperactivity and self-administration in rats. Pharmacol Biochem Behav 77:745–750
Daniela E, Gittings D, Schenk S (2006) Conditioning following repeated exposure to MDMA in rats: role in the maintenance of MDMA self-administration. Behav Neurosci 120:1144–1150
Schenk S, Foote J, Aronsen D, Bukholt N, Highgate Q, Van de Wetering R, Webster J (2016) Serotonin antagonists fail to alter MDMA self-administration in rats. Pharmacol Biochem Behav 148:38–45
Reveron ME, Maier EY, Duvauchelle CL (2006) Experience-dependent changes in temperature and behavioral activity induced by MDMA. Physiol Behav 89:358–363
Schenk S, Colussi-Mas J, Do J, Bird J (2012) Profile of MDMA self-administration from a large cohort of rats: MDMA develops a profile of dependence with extended testing. J Drug Alcohol Res 1:1–6
Cornish JL, Shahnawaz Z, Thompson MR, Wong S, Morley KC, Hunt GE, McGregor IS (2003) Heat increases 3,4-methylenedioxymethamphetamine self-administration and social effects in rats. Eur J Pharmacol 482:339–341
Feduccia AA, Kongovi N, Duvauchelle CL (2010) Heat increases MDMA-enhanced NAcc 5-HT and body temperature, but not MDMA self-administration. Eur Neuropsychopharmacol 20:884–894
Roberts DC, Brebner K, Vincler M, Lynch WJ (2002) Patterns of cocaine self-administration in rats produced by various access conditions under a discrete trials procedure. Drug Alcohol Depend 67:291–299
Aarde SM, Miller ML, Creehan KM, Vandewater SA, Taffe MA (2015) One day access to a running wheel reduces self-administration of d-methamphetamine, MDMA and methylone. Drug Alcohol Depend 151:151–158
Roth ME, Carroll ME (2004) Sex differences in the escalation of intravenous cocaine intake following long- or short-access to cocaine self-administration. Pharmacol Biochem Behav 78:199–207
Smith MA, Walker KL, Cole KT, Lang KC (2011) The effects of aerobic exercise on cocaine self-administration in male and female rats. Psychopharmacology (Berl) 218:357–369
Reichel CM, Chan CH, Ghee SM, See RE (2012) Sex differences in escalation of methamphetamine self-administration: cognitive and motivational consequences in rats. Psychopharmacology (Berl) 223:371–380
Roth ME, Carroll ME (2004) Sex differences in the acquisition of IV methamphetamine self-administration and subsequent maintenance under a progressive ratio schedule in rats. Psychopharmacology (Berl) 172:443–449
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
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
Cornish JL, Clemens KJ, Thompson MR, Callaghan PD, Dawson B, McGregor IS (2008) High ambient temperature increases intravenous methamphetamine self-administration on fixed and progressive ratio schedules in rats. J Psychopharmacol 22:100–110
Huang PK, Aarde SM, Angrish D, Houseknecht KL, Dickerson TJ, Taffe MA (2012) Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats. Drug Alcohol Depend 126:168–175
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
Watterson LR, Hood L, Sewalia K, Tomek SE, Yahn S, Johnson CT, Wegner S, Blough BE, Marusich JA, Olive MF (2012) The Reinforcing and Rewarding effects of methylone, a synthetic cathinone commonly found in “bath salts”. J Addict Res Ther S9(002):1–8
Nguyen JD, Grant Y, Creehan KM, Vandewater SA, Taffe MA (2016) Escalation of intravenous self-administration of methylone and mephedrone under extended access conditions. Addict Biol. doi:10.1111/adb.12398
Clayton JA, Collins FS (2014) Policy: NIH to balance sex in cell and animal studies. Nature 509:282–283
DeVito EE, Babuscio TA, Nich C, Ball SA, Carroll KM (2014) Gender differences in clinical outcomes for cocaine dependence: randomized clinical trials of behavioral therapy and disulfiram. Drug Alcohol Depend 145:156–167
Westermeyer J, Boedicker AE (2000) Course, severity, and treatment of substance abuse among women versus men. Am J Drug Alcohol Abuse 26:523–535
Kim JY, Fendrich M (2002) Gender differences in juvenile arrestees’ drug use, self-reported dependence, and perceived need for treatment. Psychiatr Serv 53:70–75
Rawson RA, Gonzales R, Obert JL, McCann MJ, Brethen P (2005) Methamphetamine use among treatment-seeking adolescents in Southern California: participant characteristics and treatment response. J Subst Abuse Treat 29:67–74
Bruno R, Matthews AJ, Topp L, Degenhardt L, Gomez R, Dunn M (2009) Can the severity of dependence scale be usefully applied to ‘ecstasy’? Neuropsychobiology 60:137–147
Smith MA, Pennock MM, Walker KL, Lang KC (2012) Access to a running wheel decreases cocaine-primed and cue-induced reinstatement in male and female rats. Drug Alcohol Depend 121:54–61
Huskinson SL, Naylor JE, Rowlett JK, Freeman KB (2014) Predicting abuse potential of stimulants and other dopaminergic drugs: overview and recommendations. Neuropharmacology 87C:66–80
Papaseit E, Perez-Mana C, Mateus JA, Pujadas M, Fonseca F, Torrens M, Olesti E, de la Torre R, Farre M (2016) Human pharmacology of mephedrone in comparison with MDMA. Neuropsychopharmacology 41(11):2704–2713
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
Martinez-Clemente J, Lopez-Arnau R, Carbo M, Pubill D, Camarasa J, Escubedo E (2013) Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics. Psychopharmacology (Berl) 229:295–306
Iversen L, Gibbons S, Treble R, Setola V, Huang XP, Roth BL (2013) Neurochemical profiles of some novel psychoactive substances. Eur J Pharmacol 700:147–151
Katz JL, T-P S, Hiranita T, Hayashi T, Tanda G, Kopajtic T, Tsai S-Y (2011) A role for sigma receptors in stimulant self administration and addiction. Pharmaceuticals (Basel) 4:880–914
Bonano JS, Glennon RA, De Felice LJ, Banks ML, Negus SS (2014) Abuse-related and abuse-limiting effects of methcathinone and the synthetic “bath salts” cathinone analogs methylenedioxypyrovalerone (MDPV), methylone and mephedrone on intracranial self-stimulation in rats. Psychopharmacology (Berl) 231(1):199–207
Gatch MB, Taylor CM, Forster MJ (2013) Locomotor stimulant and discriminative stimulus effects of ‘bath salt’ cathinones. Behav Pharmacol 24(5–6):437–447
Acknowledgments
Preparation of this review was supported in part by grants provided by the US National Institutes of Health (DA024105; DA024705) which had no further input on the content or decision to publish. The authors are grateful for the efforts of research technical staff Sophia A. Vandewater, Kevin M. Creehan, and Yanabel Grant who have assisted tremendously over the years with our efforts to understand the effects of entactogen and non-entactogen psychostimulant drugs.
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Aarde, S.M., Taffe, M.A. (2016). Predicting the Abuse Liability of Entactogen-Class, New and Emerging Psychoactive Substances via Preclinical Models of Drug Self-administration. 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_54
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