Psychopharmacology

, Volume 188, Issue 2, pp 193–200 | Cite as

Reinforcing effects of smoked methamphetamine in rhesus monkeys

Original Investigation

Abstract

Rationale

The occurrence of methamphetamine (METH) use by the smoking route is increasing. A nonhuman primate model for examining the reinforcing effects of smoked METH would be valuable for testing potential interventions for treating METH abuse disorders.

Objective

The purpose of the present study was to examine the reinforcing effects of smoked METH in monkeys.

Materials and methods

Four rhesus monkeys were trained to smoke cocaine (COC) under a chain fixed-ratio (FR) 64 lever press, FR 5 inhalation schedule of reinforcement. Upon observing stable levels of self-administration, METH was substituted for COC and a dose-response function for METH (0.08–0.8 mg/kg) was determined. Subsequently, the number of deliveries of COC (1 mg/kg), and 0.2 and 0.8 mg/kg METH were examined across increasing response requirements.

Results

METH was dose-dependently self-administered. Higher doses of METH (0.2, 0.4, and 0.8 mg/kg) produced asymptotic levels of responding that were slightly lower than those obtained with 1 mg/kg COC. Numbers of deliveries of COC and METH decreased as response requirement increased. METH, however, maintained fewer deliveries than 1 mg/kg COC at most response requirements.

Conclusions

METH is readily self-administered by smoking in rhesus monkeys when substituted for COC. METH may have a lower reinforcing strength than COC, but further research is needed to fully characterize its relative reinforcing strength.

Keywords

Methamphetamine Cocaine Rhesus monkey Smoking Relative persistence Self-administration 

References

  1. Balster RL, Schuster CR (1973a) A comparison of d-amphetamine, l-amphetamine, and methamphetamine self-administration in rhesus monkeys. Pharmacol Biochem Behav 1:67–71PubMedCrossRefGoogle Scholar
  2. Balster RL, Schuster CR (1973b) Fixed-interval schedule of cocaine reinforcement: effect of dose and infusion duration. J Exp Anal Behav 20:119–129PubMedCrossRefGoogle Scholar
  3. Balster RL, Kilbey MM, Ellinwood EH Jr (1976) Methamphetamine self-administration in the cat. Psychopharmacologia 46:229–233PubMedCrossRefGoogle Scholar
  4. Beardsley PM, Balster RL (1993) The effects of delay of reinforcement and dose on the self-administration of cocaine and procaine in rhesus monkeys. Drug and Alcohol Dependence 34:37–43PubMedCrossRefGoogle Scholar
  5. Bickel WK, Madden GJ, DeGrandpre RJ (1997) Modeling the effects of combined behavioral and pharmacological treatment on cigarette smoking: behavioral-economic analyses. Exp Clin Psychopharmacol 5:334–343PubMedCrossRefGoogle Scholar
  6. Carroll ME, Krattiger KL, Gieske D, Sadoff D (1990) Cocaine-base smoking in rhesus monkeys: reinforcing and physiological effects. Psychopharmacology (Berl) 102:443–450CrossRefGoogle Scholar
  7. Carroll ME, Bickel WK, Higgins ST (2001) Nondrug incentives to treat drug abuse: laboratory and clinical developments. In: Overmier JB (ed) Animal research and human health. American Psychological Association, Washington D.C., pp 139–154CrossRefGoogle Scholar
  8. Comer SD, Hunt VR, Carroll ME (1994) Effects of concurrent saccharin availability and buprenorphine pretreatment on demand for smoked cocaine base in rhesus monkeys. Psychopharmacology (Berl) 115:15–23CrossRefGoogle Scholar
  9. Cook CE, Jeffcoat AR, Hill JM, Pugh DE, Patetta PK, Sadler BM, White WR, Perez-Reyes M (1993) Pharmacokinetics of methamphetamine self-administered to human subjects by smoking S-(+)-methamphetamine hydrochloride. Drug Metab Dispos 21:717–723PubMedGoogle Scholar
  10. Cosgrove KP, Carroll ME (2002) Effects of bremazocine on self-administration of smoked cocaine base and orally delivered ethanol, phencyclidine, saccharin, and food in rhesus monkeys: a behavioral economic analysis. J Pharmacol Exp Ther 301:993–1002PubMedCrossRefGoogle Scholar
  11. Czoty PW, Makriyannis A, Bergman J (2004) Methamphetamine discrimination and in vivo microdialysis in squirrel monkeys. Psychopharmacology (Berl) 175:170–178CrossRefGoogle Scholar
  12. Evans SM, Nasser J, Comer SD, Foltin RW (2003) Smoked heroin in rhesus monkeys: effects of heroin extinction and fluid availability on measures of heroin seeking. Pharmacol Biochem Behav 74:723–737PubMedCrossRefGoogle Scholar
  13. Foltin RW, Evans SM (2001) Location preference related to smoked heroin self-administration by rhesus monkeys. Psychopharmacology (Berl) 155:419–425CrossRefGoogle Scholar
  14. Hart CL, Ward AS, Haney M, Foltin RW, Fischman MW (2001) Methamphetamine self-administration by humans. Psychopharmacology (Berl) 157:75–81CrossRefGoogle Scholar
  15. Hatsukami D, Keenan R, Carroll M, Colon E, Geiske D, Wilson B, Huber M (1990) A method for delivery of precise doses of smoked cocaine-base to humans. Pharmacol Biochem Behav 36:1–7PubMedCrossRefGoogle Scholar
  16. Hatsukami D, Thompson TN, Pentel P, Flygare B, Carroll M (1994) Self-administration of smoked cocaine. Exp Clin Psychopharmacol 2:115–125CrossRefGoogle Scholar
  17. Lile JA, Wang Z, Woolverton WL, France JE, Gregg TC, Davies HM, Nader MA (2003) The reinforcing efficacy of psychostimulants in rhesus monkeys: the role of pharmacokinetics and pharmacodynamics. J Pharmacol Exp Ther 307:356–366PubMedCrossRefGoogle Scholar
  18. Mattox AJ, Carroll ME (1996) Smoked heroin self-administration in rhesus monkeys. Psychopharmacology (Berl) 125:195–201CrossRefGoogle Scholar
  19. Mattox AJ, Thompson SS, Carroll ME (1997) Smoked heroin and cocaine base (speedball) combinations in rhesus monkeys. Exp Clin Psychopharmacol 5:113–118PubMedCrossRefGoogle Scholar
  20. Meisch RA (2000) Relative persistence of behavior: a fundamental measure of relative reinforcing effects. Exp Clin Psychopharmacol 8:333–349PubMedCrossRefGoogle Scholar
  21. Nelson RA, Boyd SJ, Ziegelstein RC, Herning R, Cadet JL, Henningfield JE, Schuster CR, Contoreggi C, Gorelick DA (2006) Effect of rate of administration on subjective and physiological effects of intravenous cocaine in humans. Drug Alcohol Depend 82:19–24PubMedCrossRefGoogle Scholar
  22. Newton TF, De La Garza R 2nd, Kalechstein AD, Nestor L (2005) Cocaine and methamphetamine produce different patterns of subjective and cardiovascular effects. Pharmacol Biochem Behav 82:90–97PubMedCrossRefGoogle Scholar
  23. Panlilio LV, Schindler CW (2000) Self-administration of remifentanil, an ultra-short acting opioid, under continuous and progressive-ratio schedules of reinforcement in rats. Psychopharmacology (Berl) 150:61–66CrossRefGoogle Scholar
  24. Perez-Reyes M, White WR, McDonald SA, Hill JM, Jeffcoat AR, Cook CE (1991) Clinical effects of methamphetamine vapor inhalation. Life Sci 49:953–959PubMedCrossRefGoogle Scholar
  25. Rodefer JS, Mattox AJ, Thompson SS, Carroll ME (1997) Effects of buprenorphine and an alternative nondrug reinforcer, alone and in combination on smoked cocaine self-administration in monkeys. Drug Alcohol Depend 45:21–29PubMedCrossRefGoogle Scholar
  26. 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) 172:443–449CrossRefGoogle Scholar
  27. SAMHSA (2005a) Summary of findings of stimulant use from the 2003 National Survey on Drug Use and Health Report. Office of Applied Studies, NHSDA, DHHS, Rockville, MD. http://oas.samhsa.gov/2k5/stimulants/stimulants.htm
  28. SAMHSA (2005b) The DASIS report: smoked methamphetamine/amphetamines 1992–2002. Office of Applied Studies, NHSDA, DHHS, Rockville, MD. http://oas.samhsa.gov/2k4/methSmoked/methSmoked.htm
  29. 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 31:351–362PubMedCrossRefGoogle Scholar
  30. Winger G, Hursh SR, Casey KL, Woods JH (2002) Relative reinforcing strength of three N-methyl-d-aspartate antagonists with different onsets of action. J Pharmacol Exp Ther 301:690–697PubMedCrossRefGoogle Scholar
  31. Woolverton WL, Wang Z (2004) Relationship between injection duration, transporter occupancy and reinforcing strength of cocaine. Eur J Pharmacol 486:251–257PubMedCrossRefGoogle Scholar
  32. Woolverton WL, Cervo L, Johanson CE (1984) Effects of repeated methamphetamine administration on methamphetamine self-administration in rhesus monkeys. Pharmacol Biochem Behav 21:737–741PubMedCrossRefGoogle Scholar
  33. Woolverton WL, Ranaldi R, Wang Z, Ordway GA, Paul IA, Petukhov P, Kozikowski A (2002) Reinforcing strength of a novel dopamine transporter ligand: pharmacodynamic and pharmacokinetic mechanisms. J Pharmacol Exp Ther 303:211–217PubMedCrossRefGoogle Scholar
  34. Yokel RA, Pickens R (1973) Self-administration of optical isomers of amphetamine and methylamphetamine by rats. J Pharmacol Exp Ther 187:27–33PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Department of PsychiatryUniversity of Minnesota Medical SchoolMinneapolisUSA

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