Psychopharmacology

, Volume 232, Issue 11, pp 1867–1877

Binge-like acquisition of 3,4-methylenedioxypyrovalerone (MDPV) self-administration and wheel activity in rats

  • S. M. Aarde
  • P. K. Huang
  • T. J. Dickerson
  • M. A. Taffe
Original Investigation

Abstract

Rationale

Lack of access to conventional sources of reinforcement has been proposed as a risk factor for substance abuse in lower socioeconomic populations. There is laboratory evidence that behavioral alternatives (enrichment or exercise) and alternative reinforcers (e.g., sweetened solutions) can reduce self-administration of a variety of drugs.

Objectives

The objective of this study is to determine if drug self-administration could devalue wheel activity in an animal model.

Methods

Male Wistar rats were trained to self-administer 3,4-methylenedioxypyrovalerone (MDPV; “bath salts”), 0.05 mg/kg/infusion, i.v., with concurrent access to a running wheel that was either locked (LW) or unlocked (UW).

Results

MDPV intake steadily increased across the 20-session acquisition interval but did not differ significantly between UW and LW groups. Mean wheel rotations declined significantly across the acquisition interval in the UW group. Of the rats that acquired self-administration, 60 % engaged in a binge-like behavior at the initiation of acquisition; intake was limited only by post-reinforcement time-out. The binge rats had higher post-acquisition levels of drug intake (even after excluding the binge session), and the UW binge rats showed a precipitous post-acquisition drop in wheel activity that was not observed in the UW no-binge rats.

Conclusions

These data confirm that MDPV is a powerful reward/reinforcer and show that a relatively high rate of intake at the onset of drug taking can devalue natural rewards (wheel activity) and can predict higher subsequent drug intake levels. Thus, limiting the intensity of initial drug exposure may attenuate subsequent drug abuse/addiction by preventing the devaluation of natural alternative rewards/reinforcers.

Keywords

Stimulants Drug abuse Exercise Self-administration Cathinone Reward 

Supplementary material

213_2014_3819_MOESM1_ESM.pdf (976 kb)
ESM 1(PDF 975 kb)

References

  1. Aarde SM, Angrish D, Barlow DJ, Wright MJ Jr, Vandewater SA, Creehan KM, Houseknecht KL, Dickerson TJ, Taffe MA (2013a) Mephedrone (4-methylmethcathinone) supports intravenous self-administration in Sprague–Dawley and Wistar rats. Addict Biol 18:786–799CrossRefPubMedCentralPubMedGoogle Scholar
  2. Aarde SM, Huang PK, Creehan KM, Dickerson TJ, Taffe MA (2013b) The novel recreational drug 3,4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: self-administration and locomotor activity in rats. Neuropharmacology 71:130–140CrossRefPubMedCentralPubMedGoogle Scholar
  3. Ahmed SH, Koob GF (1998) Transition from moderate to excessive drug intake: change in hedonic set point. Science 282:298–300CrossRefPubMedGoogle Scholar
  4. Ahmed SH, Koob GF (1999) Long-lasting increase in the set point for cocaine self-administration after escalation in rats. Psychopharmacology 146:303–312CrossRefPubMedGoogle Scholar
  5. Ahmed SH, Lenoir M, Guillem K (2013) Neurobiology of addiction versus drug use driven by lack of choice. Curr Opin Neurobiol 23:581–587CrossRefPubMedGoogle Scholar
  6. Anker JJ, Brimijoin S, Gao Y, Geng L, Zlebnik NE, Parks RJ, Carroll ME (2012) Cocaine hydrolase encoded in viral vector blocks the reinstatement of cocaine seeking in rats for 6 months. Biol Psychiatry 71:700–705CrossRefPubMedCentralPubMedGoogle Scholar
  7. Anthony JC, Warner LA, Kessler RC (1994) Comparative epidemiology of dependence on tobacco, alcohol, controlled substances and inhalants: basic findings from the national comorbidity survey. Exp Clin Pyschopharm 2:244–268CrossRefGoogle Scholar
  8. Bauer CT, Banks ML, Blough BE, Negus SS (2013) Use of intracranial self-stimulation to evaluate abuse-related and abuse-limiting effects of monoamine releasers in rats. Br J Pharmacol 168:850–862CrossRefPubMedCentralPubMedGoogle Scholar
  9. 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: Off Publ Am Coll Neuropsychopharmacology 38:552–562CrossRefGoogle Scholar
  10. Belke TW (2010) Exclusive preference develops less readily on concurrent ratio schedules with wheel-running than with sucrose reinforcement. J Exp Anal Behav 94:135–158CrossRefPubMedCentralPubMedGoogle Scholar
  11. Belke TW, Hancock SD (2003) Responding for sucrose and wheel-running reinforcement: effects of sucrose concentration and wheel-running reinforcer duration. J Exp Anal Behav 79:243–265CrossRefPubMedCentralPubMedGoogle Scholar
  12. Belke TW, Heyman GM (1994) A matching law analysis of the reinforcing efficacy of wheel running in rats. Anim Learning Behav 22(3):267–274CrossRefGoogle Scholar
  13. Benzie F, Hekman K, Cameron L, Wade DR, Smolinske S (2011) Emergency department visits after use of a drug sold as “bath salts”—Michigan, November 13, 2010–March 31, 2011. MMWR Morb Mortal Wkly Rep 60:624–627Google Scholar
  14. Bluelight (2006) MDPV Megathread http://www.bluelight.ru/vb/threads/278421-MDPV-Megathread. Accessed 11 Apr 2010
  15. Borek HA, Holstege CP (2012) Hyperthermia and multiorgan failure after abuse of “bath salts” containing 3,4-methylenedioxypyrovalerone. Ann Emerg Med ;60(1):103–105. doi:10.1016/j.annemergmed
  16. Bradbury S, Bird J, Colussi-Mas J, Mueller M, Ricaurte G, Schenk S (2013) Acquisition of MDMA self-administration: pharmacokinetic factors and MDMA-induced serotonin release. Addict Biol. doi:10.1111/j.1369-1600.2012.00477 PubMedGoogle Scholar
  17. 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 227(3):493–499. doi:10.1007/s00213-013-2967-2
  18. Carroll ME, Lac ST (1993) Autoshaping i.v. cocaine self-administration in rats: effects of nondrug alternative reinforcers on acquisition. Psychopharmacology 110:5–12CrossRefPubMedGoogle Scholar
  19. Collier G, Hirsch E (1971) Reinforcing properties of spontaneous activity in the rat. J Comp Physiol Psychol 77:155–160CrossRefPubMedGoogle Scholar
  20. Cosgrove KP, Hunter RG, Carroll ME (2002) Wheel-running attenuates intravenous cocaine self-administration in rats: sex differences. Pharmacol Biochem Behav 73:663–671CrossRefPubMedGoogle Scholar
  21. Deehan GA Jr, Palmatier MI, Cain ME, Kiefer SW (2011) Differential rearing conditions and alcohol-preferring rats: consumption of and operant responding for ethanol. Behav Neurosci 125:184–193CrossRefPubMedGoogle Scholar
  22. El Rawas R, Thiriet N, Lardeux V, Jaber M, Solinas M (2009) Environmental enrichment decreases the rewarding but not the activating effects of heroin. Psychopharmacology 203:561–570CrossRefPubMedGoogle Scholar
  23. Eshleman AJ, Wolfrum KM, Hatfield MG, Johnson RA, Murphy KV, Janowsky A (2013) Substituted methcathinones differ in transporter and receptor interactions. Biochem Pharmacol 85:1803–1815CrossRefPubMedCentralPubMedGoogle Scholar
  24. Flory K, Lynam D, Milich R, Leukefeld C, Clayton R (2004) Early adolescent through young adult alcohol and marijuana use trajectories: early predictors, young adult outcomes, and predictive utility. Dev Psychopathol 16:193–213PubMedGoogle Scholar
  25. Fowler SC, Covington HE 3rd, Miczek KA (2007) Stereotyped and complex motor routines expressed during cocaine self-administration: results from a 24-h binge of unlimited cocaine access in rats. Psychopharmacology 192:465–478CrossRefPubMedGoogle Scholar
  26. Gipson CD, Beckmann JS, El-Maraghi S, Marusich JA, Bardo MT (2011) Effect of environmental enrichment on escalation of cocaine self-administration in rats. Psychopharmacology 214:557–566CrossRefPubMedCentralPubMedGoogle Scholar
  27. 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 126:168–175CrossRefPubMedCentralPubMedGoogle Scholar
  28. Hundt AG, Premack D (1963) Running as both a positive and negative reinforcer. Science 142:1087–1088CrossRefPubMedGoogle Scholar
  29. Juon HS, Fothergill KE, Green KM, Doherty EE, Ensminger ME (2011) Antecedents and consequences of marijuana use trajectories over the life course in an African American population. Drug Alcohol Depend 118:216–223CrossRefPubMedCentralPubMedGoogle Scholar
  30. Lenoir M, Serre F, Cantin L, Ahmed SH (2007) Intense sweetness surpasses cocaine reward. PLoS ONE 2:e698CrossRefPubMedCentralPubMedGoogle Scholar
  31. Lenoir M, Cantin L, Vanhille N, Serre F, Ahmed SH (2013) Extended heroin access increases heroin choices over a potent nondrug alternative. Neuropsychopharmacology 38(7):1209–1220. doi:10.1038/npp.2013.17
  32. Loh EA, Roberts DC (1990) Break-points on a progressive ratio schedule reinforced by intravenous cocaine increase following depletion of forebrain serotonin. Psychopharmacology 101:262–266CrossRefPubMedGoogle Scholar
  33. Maume MO, Ousey GC, Beaver K (2005) Cutting the grass: a reexamination of the link between marital attachment, delinquent peers and desistance from marijuana use. J Quant Criminol 21:27–53CrossRefGoogle Scholar
  34. 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 121:90–96CrossRefPubMedCentralPubMedGoogle Scholar
  35. Miller ML, Moreno AY, Aarde SM, Creehan KM, Vandewater SA, Vaillancourt BD, Wright MJ Jr, Janda KD, Taffe MA (2013) A methamphetamine vaccine attenuates methamphetamine-induced disruptions in thermoregulation and activity in rats. Biol Psychiatry 73:721–728CrossRefPubMedCentralPubMedGoogle Scholar
  36. Morgan D, Smith MA, Roberts DC (2005) Binge self-administration and deprivation produces sensitization to the reinforcing effects of cocaine in rats. Psychopharmacology 178:309–316CrossRefPubMedGoogle Scholar
  37. 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(5):534–535. doi:10.1038/mp.2013.75
  38. Pierce WD, Epling WF, Boer DP (1986) Deprivation and satiation: the interrelations between food and wheel running. J Exp Anal Behav 46:199–210CrossRefPubMedCentralPubMedGoogle Scholar
  39. Premack D, Schaeffer RW, Hundt A (1964) Reinforcement of drinking by running: effect of fixed ratio and reinforcement time. J Exp Anal Behav 7:91–96CrossRefPubMedCentralPubMedGoogle Scholar
  40. Puhl MD, Blum JS, Acosta-Torres S, Grigson PS (2012) Environmental enrichment protects against the acquisition of cocaine self-administration in adult male rats, but does not eliminate avoidance of a drug-associated saccharin cue. Behav Pharmacol 23:43–53CrossRefPubMedCentralPubMedGoogle Scholar
  41. Richman A (1977) The epidemiology of drug abuse: current issues. Ecological studies of narcotic addiction. NIDA research monograph: 173–96Google Scholar
  42. 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 67:291–299CrossRefPubMedGoogle Scholar
  43. Ross EA, Reisfield GM, Watson MC, Chronister CW, Goldberger BA (2012) Psychoactive “bath salts” intoxication with methylenedioxypyrovalerone. Am J Med 125(9):854–858. doi:10.1016/j.amjmed.2012.02.019
  44. Schramm-Sapyta NL, Walker QD, Caster JM, Levin ED, Kuhn CM (2009) Are adolescents more vulnerable to drug addiction than adults? Evidence from animal models. Psychopharmacology 206:1–21CrossRefPubMedCentralPubMedGoogle Scholar
  45. Shohat-Ophir G, Kaun KR, Azanchi R, Mohammed H, Heberlein U (2012) Sexual deprivation increases ethanol intake in Drosophila. Science 335:1351–1355CrossRefPubMedCentralPubMedGoogle Scholar
  46. 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. Brit J Pharmacol 168:458–470CrossRefGoogle Scholar
  47. Solinas M, Chauvet C, Thiriet N, El Rawas R, Jaber M (2008) Reversal of cocaine addiction by environmental enrichment. Proc Natl Acad Sci U S A 105:17145–17150CrossRefPubMedCentralPubMedGoogle Scholar
  48. Tornatzky W, Miczek KA (2000) Cocaine self-administration “binges”: transition from behavioral and autonomic regulation toward homeostatic dysregulation in rats. Psychopharmacology 148:289–298CrossRefPubMedGoogle Scholar
  49. Wall M, Schmidt E, Sarang A, Atun R, Renton A (2011) Sex, drugs and economic behaviour in Russia: a study of socio-economic characteristics of high risk populations. Int J Drug Policy 22:133–139CrossRefPubMedGoogle Scholar
  50. 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 19:165–174CrossRefPubMedCentralPubMedGoogle Scholar
  51. Wojnicki FH, Johnson DS, Corwin RL (2008) Access conditions affect binge-type shortening consumption in rats. Physiol Behav 95:649–657CrossRefPubMedCentralPubMedGoogle Scholar
  52. Wyman JF, Lavins ES, Engelhart D, Armstrong EJ, Snell KD, Boggs PD, Taylor SM, Norris RN, Miller FP (2013) Postmortem tissue distribution of MPDV following lethal intoxication by “bath salts”. J Anal Toxicol 37:182–185CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • S. M. Aarde
    • 1
  • P. K. Huang
    • 1
  • T. J. Dickerson
    • 2
  • M. A. Taffe
    • 1
  1. 1.Committee on the Neurobiology of Addictive DisordersThe Scripps Research InstituteLa JollaUSA
  2. 2.Department of ChemistryThe Scripps Research InstituteLa JollaUSA

Personalised recommendations