The Dependence-Producing Properties of Psychomotor Stimulants

  • J. E. Villarreal
  • L. A. Salazar
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 55 / 2)


This review deals with a singular form of pathology induced by certain drugs, including some of the group that are currently classified as psychomotor stimulants. For historical reasons, this form of pathology is now generically called drug dependence, with subclasses defined in terms of the type of pharmacologic agent that generates or maintains the disorder. Other terms such as toxicomania, habituation, or addiction have been employed for the disease. It is possible that its name will change again in the future as the new, growing knowledge about its nature develops more fully. The main objective of this chapter is to review the disease of dependence to psychomotor stimulants as well as the results of experimental work aimed at understanding and measuring the dependence-producing properties that these drugs possess. Simultaneous attention to these two levels of study — analysis of dependence as a disease and experimental analysis of drug actions related to dependence production — has been deemed necessary to maintain the complete perspective that the subject requires.


Rhesus Monkey Drug Dependence Progressive Ratio Concurrent Schedule Psychomotor Stimulant 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Balster, R.L., Schuster, C.R.: Fixed-interval schedule of cocaine reinforcement: effect of dose and infusion duration. J. Exp. Anal. Behav. 20, 119–129 (1973)PubMedCrossRefGoogle Scholar
  2. Balster, R.L., Kilbey, M.M., Ellinwood, jr., E.H.: Methamphetamine self-administration in the cat. Psychopharmacologia (Berl.) 46, 229–233 (1976)CrossRefGoogle Scholar
  3. Bedford, J.A., Bailey, L.P., Wilson, M.C.: Cocaine reinforced progressive-ratio performance in the rhesus monkey. Pharmacol. Biochem. Behav. 9, 631–638 (1978)PubMedCrossRefGoogle Scholar
  4. Bedford, J.A., Borne, R.F., Wilson, M.C.: Comparative behavioral profile of cocaine and nor-cocaine in rats and monkeys. Pharmacol. Biochem. Behav. 13, 69–75 (1980)PubMedCrossRefGoogle Scholar
  5. Bejerot, N.: spivn In: Sjöqvist, F., Tottie, M. (eds.): Abuse of central stimulants, p. 298. Stockholm: Almqvist & Wiksell 1969Google Scholar
  6. Boissier de Sauvages, F.: Nosologie methodique. French translation by Nicolas, M. (1771) of the original Latin version of 1762. Facsimile at the National Library of Medicine, Washington, D.C.Google Scholar
  7. Carey, J.T., Mandel, J.: A San Francisco bay area “speed” scene. J. Hlth. Soc. Behav. 9, 164–174 (1968)CrossRefGoogle Scholar
  8. Catania, A.C.: Drug effects and concurrent performances. Pharmacol. Rev. 27, 385–394 (1976)Google Scholar
  9. Clineschmidt, B.V., Hanson, H.M., Pflueger, A.B., McGuffin, J.C.: Anorexigenic and ancillary actions of MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine; CPP). Psychopharmacology 55, 27–33 (1977)PubMedCrossRefGoogle Scholar
  10. Cytawa, J., Jurkowlaniec, E., Biatowas, J.: Positive reinforcement produced by noradrenergic stimulation of the hypothalamus in rats. Physiol. Behav. 25, 615–619 (1980)PubMedCrossRefGoogle Scholar
  11. Deneau, G.A., Yanagita, T., Seevers, M.H.: Self-administration of psychoactive substances by the monkey: a measure of psychological dependence. Psychopharmacologia (Berl.) 16, 30–48 (1969)CrossRefGoogle Scholar
  12. De V. Cotten, M. (ed): Symposium on control of drug taking behavior by schedules of reinforcement. Pharmacol. Rev. 27, 291–548 (1976)Google Scholar
  13. Dougherty, J., Pickens, R.: Fixed-interval schedules of intravenous cocaine presentation in rats. J. Exp. Anal. Behav. 20, 111–118 (1973)PubMedCrossRefGoogle Scholar
  14. Dougherty, J., Pickens, R.: Pharmacokinetics of intravenous cocaine selfinjection. In: Mulé, S.J. (ed.) Cocaine: chemical, biological, clinical, social, and treatment aspects. Cleveland, Ohio: CRC Press 1976Google Scholar
  15. Down, D.A., Woods, J.H.: Food- and drug-reinforced responding: effects of DITA and d-am-phetamine. Psychopharmacologia (Berl) 43, 13–17 (1975)CrossRefGoogle Scholar
  16. Elsmore, T.F., Fletcher, G.V., Conrad, D.G., Sodetz, F.J.: Reduction of heroin intake in baboons by an economic constraint. Pharmacol. Biochem. Behav. 13, 729–731 (1980)PubMedCrossRefGoogle Scholar
  17. Estrada, U., Villarreal, J.E., Schuster, C.R.: Self-administration of stimulant drugs as a function of the dose per injection. Minutes of the twenty-seventh meeting of the CPDD. pp. 5056–5059. National Academy of Sciences, Washington, D.C. 1967Google Scholar
  18. Findley, J.D., Robinson, W.W., Gilliam, W.: A restraint system for chronic study of the baboon. J. Exp. Anal. Behav. 15, 69–71 (1971)PubMedCrossRefGoogle Scholar
  19. Findley, J.D., Robinson, W.W., Peregrino, L.: Addiction to secobarbital and chlordiazepoxide in the rhesus monkey by means of self-infusion preference procedure. Psychopharmacologia (Berl.) 26, 93–114 (1972)CrossRefGoogle Scholar
  20. Goldberg, S.R.: Comparable behavior maintained under fixed-ratio and second-order schedules of food presentation, cocaine injection or d-amphetamine injection in the squirrel monkey. J. Pharmacol. Exp. Ther. 186, 18–30 (1973)PubMedGoogle Scholar
  21. Goldberg, S.R., Morse, W.H., Goldberg, D.M.: Behavior maintained under a second-order schedule by intramuscular injection of morphine or cocaine in rhesus monkeys. J. Pharmacol. Exp. Ther. 199, 278–286 (1976)PubMedGoogle Scholar
  22. Griffith, J.D.: A study of illicit amphetamine drug traffic in Oklahoma City. Amer. J. Psychiat. 123, 560–569 (1966)PubMedGoogle Scholar
  23. Griffith, J.D.: Amphetamine dependence; clinical features. In: Martin, W.R. (ed.): Drug addiction II. pp. 277–304. Handb. exp. pharm. Vol. 45/II. Berlin Heidelberg New York: Springer-Verlag 1977Google Scholar
  24. Griffiths, R.R., Findley, J.D., Brady, J.V., Dolan-Gutcher, K., Robinson, W.: Comparison of progressive-ratio performance maintained by cocaine, methylphenidate, and secobarbital. Psychopharmacologia (Berl.) 43, 81–83 (1975)CrossRefGoogle Scholar
  25. Griffiths, R.R., Winger, G., Brady, J.V., Snell, J.D.: Comparison of behavior maintained by infusions of eight phenylethylamines in baboons. Psychopharmacology 50, 251–258 (1976)PubMedCrossRefGoogle Scholar
  26. Griffiths, R.R., Brady, J.V., Snell, J.D.: Progressive-ratio performance maintained by drug infusions: comparison of cocaine, diethylpropion, chlorphentermine, and fenfluramine. Psychopharmacology (Berl.) 56, 5–13 (1978a)CrossRefGoogle Scholar
  27. Griffiths, R.R., Brady, J.V., Snell, J.D.: Relationship between anoretic and reinforcing properties of appetite suppressant drugs: implications for assessment of abuse liability. Biol. Psychiat. 13, 283–290 (1978b)Google Scholar
  28. Griffiths, R.R., Bradford, L. DiAnne, Brady, J.V.: Progressive ratio and fixed ratio schedules of cocaine-maintained responding in baboons. Psychopharmacology 65, 125–136 (1979)PubMedCrossRefGoogle Scholar
  29. Hawks, D., Mitcheson, M., Ogborne, A., Edwards, G.: Abuse of methylamphetamine. Brit. Med. J. 1969 II, 715–721CrossRefGoogle Scholar
  30. Herling, S., Downs, D.A., Woods, J.H.: Cocaine, d-amphetamine, and pentobarbital effects on responding maintained by food or cocaine in rhesus monkey. Psychopharmacology 64, 261–269 (1979)PubMedCrossRefGoogle Scholar
  31. Hodos, W.: Progressive ratio as a measure of reward strength. Science 134, 943–944 (1961)PubMedCrossRefGoogle Scholar
  32. Hodos, W., Kaiman, G.: Effects of increment size and reinforcer volume on progressive ratio performance. J. Exp. Anal. Behav. 6, 387–392 (1963)PubMedCrossRefGoogle Scholar
  33. Hoffmeister, F.: Negative reinforcing properties of some psychotropic drugs in drug-naive rhesus monkeys. J. Pharmacol. Exp. Ther. 192, 468–477 (1975)PubMedGoogle Scholar
  34. Hoffmeister, F.: Progressive ratio performance in the rhesus monkey maintained by opiate infusions. Psychopharmacology 62, 181–186 (1979)PubMedCrossRefGoogle Scholar
  35. Hoffmeister, F., Goldberg, S.R.: A comparison of chlorpromazine, imipramine, morphine, and d-amphetamine self-administration in cocaine-dependent rhesus monkeys. J. Pharmacol. Exp. Ther. 187, 8–14 (1973)PubMedGoogle Scholar
  36. Hoffmeister, F., Wuttke, W.: Further studies on self-administration of antipyretic analgesics with codeine in rhesus monkeys. J. Pharmacol. Exp. Ther. 193, 870–875 (1975)PubMedGoogle Scholar
  37. Hursh, S.R.: Economic concepts for the analysis of behavior. J. Exp. Anal. Behav. 34, 219–238 (1980)PubMedCrossRefGoogle Scholar
  38. Iglauer, C., Woods, J.H.: Concurrent performances: reinforcement by different doses of intravenous cocaine in rhesus monkeys. J. Exp. Anal. Behav. 22, 179–196 (1974)PubMedCrossRefGoogle Scholar
  39. Iglauer, C., Llewellyn, M.E., Woods, J.H.: Concurrent schedules of cocaine injection in rhesus monkeys: dose variations under independent and non-independent variable-interval procedures. Pharmacol. Rev. 27, 367–383 (1976)Google Scholar
  40. Jasinski, D.R., Gilbert, P.E., Vaupel, B., Risner, M.E., Cone, E.J.: Stimulant self-administration studies in dog. Progress Report from the NIDA addiction research center. Proceedings of the fortieth annual scientific meeting of the CPDD, pp. 171–177. National Academy of Sciences, Washington, D.C. 1978Google Scholar
  41. Johanson, C.E., Schuster, C.R.: A choice procedure for drug reinforcers: cocaine and methyl-phenidate in the rhesus monkey. J. Pharmacol. Exp. Ther. 193, 676–688 (1975)PubMedGoogle Scholar
  42. Johanson, C.E., Schuster, C.R.: A comparison of cocaine and diethylpropion under the different schedules of drug presentation. In: Ellinwood, E.H., Kilbey, M.M. (eds.): Cocaine and other stimulants, pp. 545–570. New York: Plenum 1976Google Scholar
  43. Johanson, C.E., Balster, R.L., Bonese, K.: Self-administration of psychomotor stimulant drugs: the effects of unlimited access. Pharmacol. Biochem. Behav. 4, 45–51 (1976a)PubMedCrossRefGoogle Scholar
  44. Johanson, C.E., Kandel, D.A., Bonese, K.: The effects of perphenazine on self-administration behavior. Pharmacol. Biochem. Behav. 4, 427–433 (1976b)PubMedCrossRefGoogle Scholar
  45. Jones, B.E., Prada, J.A.: Relapse to morphine use in dog. Psychopharmacologia (Berl.) 30, 1–12 (1973)CrossRefGoogle Scholar
  46. Kallant, O.J.: The amphetamines: toxicity and addiction. Toronto: University of Toronto Press, 1966Google Scholar
  47. Kallant, O.J.: The amphetamines: toxicity and addiction, 2nd ed. Springfield, Ill.: Thomas 1973Google Scholar
  48. Kato, M.: Epidemiology of drug dependence in Japan. In: Zarafonetis, C.J.D. (ed.): Drug abuse, pp. 67–70. Philadelphia: Lea & Febiger 1972Google Scholar
  49. Keesey, R.E., Goldstein, M.D.: Use of progressive fixed ratio procedures in the assessment of intracranial reinforcement. J. Exp. Anal. Behav. 11, 293–301 (1968)PubMedCrossRefGoogle Scholar
  50. Kelleher, R.T.: Conditioned reinforcement in second-order schedules. J. Exp. Anal. Behav. 9, 475–485 (1966)PubMedCrossRefGoogle Scholar
  51. Kelleher, R.T.: Characteristics of behavior controlled by scheduled injections of drugs. Pharmacol. Rev. 27, 307–323 (1976)Google Scholar
  52. Kelleher, R.T., Goldberg, S.R.: Fixed-interval responding under second order schedules of food presentation or cocaine injection. J. Exp. Anal. Behav. 28, 221–231 (1977)PubMedCrossRefGoogle Scholar
  53. Kramer, J.C., Fishman, V.S., Littlefield, D.C.: Amphetamine abuse. Pattern and effects of high doses taken intravenously. J. Amer. Med. Ass. 201, 305–309 (1967)CrossRefGoogle Scholar
  54. Masaki, T.: The amphetamine problem in Japan. Wld. Hlth. Org. Techn. Rep. Ser. 102, 14–21 (1956)Google Scholar
  55. Pickens, R., Thompson, T.: Self-administration of amphetamine and cocaine by rats. Minutes of the twenty-seventh meeting of the CPDD, pp. 5049–5055. National Academy of Sciences, Washington, D.C. 1967Google Scholar
  56. Pickens, R., Thompson, T.: Cocaine-reinforced behavior in rats: effects of reinforcement magnitude and fixed ratio size. J. Pharmacol. Exp. Ther. 161, 122–129 (1968)PubMedGoogle Scholar
  57. Risner, M.E.: Intravenous self-administration of d- and L-amphetamine by dog. Eur. J. Pharmacol. 32, 344–348 (1975)PubMedCrossRefGoogle Scholar
  58. Risner, M.E., Jones, B.E.: Self-administration of CNS stimulants by dog. Psychopharma-cologia (Berl.) 43, 207–213 (1975)CrossRefGoogle Scholar
  59. Risner, M.E., Jones, B.E.: Intravenous self-administration of cocaine and norcocaine by dogs. Psychopharmacology 71, 83–89 (1980)PubMedCrossRefGoogle Scholar
  60. Sánchez-Ramos, J.R., Schuster, C.R.: Second-order schedules of intravenous drug self-administration in rhesus monkeys. Pharmacol. Biochem. Behav. 7, 443–450 (1977)PubMedCrossRefGoogle Scholar
  61. Schuster, C.R., Johanson, C.E.: Behavioral studies of cathinone in monkeys and rats. In: Harris, L.S. (ed.): Problems of drug dependence, 1979. NIDA research monograph 27, pp. 324–325Google Scholar
  62. Schuster, C.R., Thompson, T.: Self-administration of and behavioral dependence on drugs. Ann. Rev. Pharmacol. 9, 483–502 (1969)PubMedCrossRefGoogle Scholar
  63. Schuster, C.R., Villarreal, J.E.: Experimental analysis of opioid dependence. In: Efron, D.H. (ed.): Psychopharmacology — a review of progress 1957–1967, pp. 811–828. Washington, D.C.: U.S. Government Printing Office 1968Google Scholar
  64. Sjöqvist, F., Tottie, M. (eds.): Abuse of central stimulants. Stockholm: Almqvist & Wiksell 1969Google Scholar
  65. Smith, R.C.: Speed and violence: compulsive methamphetamine abuse and criminality in the Haight-Ashbury District. In: Zarefonetis, C.J.D. (ed.): Drug abuse, pp. 435–448. Philadelphia: Lea & Febiger 1972Google Scholar
  66. Spealman, R.D.: Behavior maintained by termination of a schedule of self-administered cocaine. Science 204, 1231–1233 (1979)PubMedCrossRefGoogle Scholar
  67. Spealman, R.D., Goldberg, S.R.: Drug self-administration by laboratory animals: control by schedules of reinforcement. Ann. Rev. Pharmacol. Toxicol. 18, 313–339 (1978)CrossRefGoogle Scholar
  68. Stretch, R., Gerber, G.J.: A method for chronic intravenous drug administration in squirrel monkeys. Canad. J. Physiol. Pharmacol. 48, 575–581 (1970)CrossRefGoogle Scholar
  69. Sydenham, T.: The works, on acute and chronic diseases (1666–1686). Version published in English by Rush, B. in 1815. Facsimile at National Library of Medicine, Washington, D.C.Google Scholar
  70. Takahashi, R.N., Singer, G., Oei, T.P.S.: Schedule induced self-injection of D-amphetamine by naive animals. Pharmacol. Biochem. Behav. 9, 857–861 (1978)PubMedCrossRefGoogle Scholar
  71. Tessel, R.E., Woods, J.H.: Fenfluramine and N-ethylamphetamine: comparison of the reinforcing and rate-decreasing actions in the rhesus monkey. Psychopharmacologia (Berl.) 43, 239–244 (1975)CrossRefGoogle Scholar
  72. Tessel, R.E., Woods, J.H.: Meta substituted N-ethylamphetamine self-injection responding in the rhesus monkey: estructive-activity relationships. J. Pharmacol. Exp. Ther. 205, 274–281 (1978)PubMedGoogle Scholar
  73. Thompson, T., Schuster, C.R.: Morphine self-administration, food-reinforced, and avoidance behaviors in rhesus monkeys. Psychopharmacologia (Berl.) 5, 87–94 (1964)CrossRefGoogle Scholar
  74. Villarreal, J.E.: Contributions of laboratory work to the analysis and control of drug dependence. In: Bachly, P.H. (ed.): Drug abuse, data, and debate, pp. 82–103. Springfield, Ill.: Thomas 1970Google Scholar
  75. Weeks, J.R.: Experimental morphine addiction: method for automatic intravenous injections in unrestrained rats. Science 138, 143–144 (1962)PubMedCrossRefGoogle Scholar
  76. Wikler, A., Martin, W.R., Pescor, F.T., Eades, C.G.: Factors regulating oral consumption of an opioid (Etonitazine) by morphine-addicted rats. Psychopharmacologia (Berl.) 5, 55–76 (1963)CrossRefGoogle Scholar
  77. Wilson, M.C., Schuster, C.R.: The effects of chlorpromazine on psychomotor stimulant self-administration in the rhesus monkey. Psychopharmacologia 26, 115–126 (1972)PubMedCrossRefGoogle Scholar
  78. Wilson, M.C., Schuster, C.R.: Mazindol self-administration in the rhesus monkey. Pharmacol. Biochem. Behav. 4, 207–210 (1976)PubMedCrossRefGoogle Scholar
  79. Wilson, M.C., Hitomi, M., Schuster, C.R.: Psychomotor stimulant self-administration as a function of dosage per injection in the rhesus monkey. Psychopharmacologia 22, 271–281 (1971)PubMedCrossRefGoogle Scholar
  80. Wise, R.A., Yokel, R.A., DeWitt, H.: Both positive reinforcement and conditioned aversion from amphetamine and from apomorphine in rats. Science 191, 1273–1275 (1976)PubMedCrossRefGoogle Scholar
  81. Wise, R.A., Yokel, R.A., Hansson, P.A., Gerber, G.J.: Concurrent intracranial self-stimulation and amphetamine self-administration in rats. Pharmacol. Biochem. Behav. 7, 459–461 (1977)PubMedCrossRefGoogle Scholar
  82. Woods, J.H.: Behavioral effects of cocaine in animals. In: Petersen, R.C., Stillman, R.C. (eds.): Cocaine. 1977. NIDA Research monograph 13, pp. 63–95.Google Scholar
  83. Woods, J.H., Tessel, R.E.: Fenfluramine: amphetamine congener that fails to maintain drug-taking behavior in the rhesus monkey. Science 185, 1067–1069 (1974)PubMedCrossRefGoogle Scholar
  84. World Health Organization, Techn. Rep. Ser., No. 577, Evaluation of dependence liability and dependence potential of drugs 1975Google Scholar
  85. Yanagita, T.: An experimental framework for evaluation of dependence liability in various types of drugs in monkeys. Bull. Narc. 1, 25–57 (1973)Google Scholar
  86. Yanagita, T.: Brief review on the use of self-administration techniques for predicting drug abuse potential. In: Thompson, T., Unna, K. (eds.): Predicting dependence liability of stimulant and depressant drugs, pp. 231–242. Baltimore: University Park 1977Google Scholar
  87. Yanagita, T.: Studies on cathinones: cardiovascular and behavioral effects in rats and self-administration experiment in rhesus monkeys. In: Harris, L.S. (ed.): Problems of drug dependence, 1979. NIDA Research monograph 27, pp. 326–327Google Scholar
  88. Yanagita, T., Deneau, G.A., Seevers, M.H.: Evaluation of pharmacological agents in the monkey by long-term intravenous self- or programmed-adminiseration. Excerpta Med. Int. Congr. Ser. 87, 453–457 (1965)Google Scholar
  89. Young, A.M., Woods, J.H.: Behavior maintained by intravenous injection of codeine, cocaine, and etorphine in the rhesus macaque and the pigtail macaque. Psychopharmacology 70, 263–271 (1980)PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1981

Authors and Affiliations

  • J. E. Villarreal
  • L. A. Salazar

There are no affiliations available

Personalised recommendations