Skip to main content
PMC home page
Journal of the Experimental Analysis of Behavior logoLink to Journal of the Experimental Analysis of Behavior
. 2003 Jan;79(1):111–135. doi: 10.1901/jeab.2003.79-111

Stimulus control of cocaine self-administration.

Stanley J Weiss 1, David N Kearns 1, Scott I Cohn 1, Charles W Schindler 1, Leigh V Panlilio 1
PMCID: PMC1284924  PMID: 12696744

Abstract

Environmental stimuli that set the occasion wherein drugs are acquired can "trigger" drug-related behavior. Investigating the stimulus control of drug self-administration in laboratory animals should help us better understand this aspect of human drug abuse. Stimulus control of cocaine self-administration was generated here for the first time using multiple and chained schedules with short, frequently-alternating components--like those typically used to study food-maintained responding. The procedures and results are presented along with case histories to illustrate the strategies used to produce this stimulus control. All these multicomponent schedules contained variable-interval (VI) components as well as differential-reinforcement-of-other-behavior (DRO) or extinction components. Schedule parameters and unit dose were adjusted for each rat to produce stable, moderate rates in VI components, with minimal postreinforcement (infusion) pausing, and response cessation in extinction and DRO components. Whole-body drug levels on terminal baselines calculated retrospectively revealed that all rats maintained fairly stable drug levels (mean, 2.3 to 3.4 mg/kg) and molar rates of intake (approximately 6.0 mg/kg/hr). Within this range, no relation between local VI response rates and drug level was found. The stimulus control revealed in cumulative records was indistinguishable from that achieved with food under these schedules, suggesting that common mechanisms may underlie the control of cocaine- and food-maintained behavior.

Full Text

The Full Text of this article is available as a PDF (250.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahmed S. H., Koob G. F. Long-lasting increase in the set point for cocaine self-administration after escalation in rats. Psychopharmacology (Berl) 1999 Oct;146(3):303–312. doi: 10.1007/s002130051121. [DOI] [PubMed] [Google Scholar]
  2. Arroyo M., Markou A., Robbins T. W., Everitt B. J. Acquisition, maintenance and reinstatement of intravenous cocaine self-administration under a second-order schedule of reinforcement in rats: effects of conditioned cues and continuous access to cocaine. Psychopharmacology (Berl) 1998 Dec;140(3):331–344. doi: 10.1007/s002130050774. [DOI] [PubMed] [Google Scholar]
  3. Balster R. L., Schuster C. R. Fixed-interval schedule of cocaine reinforcement: effect of dose and infusion duration. J Exp Anal Behav. 1973 Jul;20(1):119–129. doi: 10.1901/jeab.1973.20-119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barbieri E. J., Ferko A. P., DiGregorio G. J., Ruch E. K. The presence of cocaine and benzoylecgonine in rat cerebrospinal fluid after the intravenous administration of cocaine. Life Sci. 1992;51(22):1739–1746. doi: 10.1016/0024-3205(92)90303-7. [DOI] [PubMed] [Google Scholar]
  5. Bickel W. K., Kelly T. H. The relationship of stimulus control to the treatment of substance abuse. NIDA Res Monogr. 1988;84:122–140. [PubMed] [Google Scholar]
  6. Caine S. B., Koob G. F. Effects of dopamine D-1 and D-2 antagonists on cocaine self-administration under different schedules of reinforcement in the rat. J Pharmacol Exp Ther. 1994 Jul;270(1):209–218. [PubMed] [Google Scholar]
  7. Caine S. B., Koob G. F. Effects of mesolimbic dopamine depletion on responding maintained by cocaine and food. J Exp Anal Behav. 1994 Mar;61(2):213–221. doi: 10.1901/jeab.1994.61-213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Childress A. R., McLellan A. T., Ehrman R. N., O'Brien C. P. Extinction of conditioned responses in abstinent cocaine or opioid users. NIDA Res Monogr. 1987;76:189–195. [PubMed] [Google Scholar]
  9. Dougherty J., Pickens R. Fixed-interval schedules of intravenous cocaine presentation in rats. J Exp Anal Behav. 1973 Jul;20(1):111–118. doi: 10.1901/jeab.1973.20-111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. ENINGER M. U. Habit summation in a selective learning problem. J Comp Physiol Psychol. 1952 Dec;45(6):604–608. doi: 10.1037/h0057144. [DOI] [PubMed] [Google Scholar]
  11. Ehrman R. N., Robbins S. J., Childress A. R., O'Brien C. P. Conditioned responses to cocaine-related stimuli in cocaine abuse patients. Psychopharmacology (Berl) 1992;107(4):523–529. doi: 10.1007/BF02245266. [DOI] [PubMed] [Google Scholar]
  12. Everitt B. J., Robbins T. W. Second-order schedules of drug reinforcement in rats and monkeys: measurement of reinforcing efficacy and drug-seeking behaviour. Psychopharmacology (Berl) 2000 Dec;153(1):17–30. doi: 10.1007/s002130000566. [DOI] [PubMed] [Google Scholar]
  13. Goeders N. E., Guerin G. F. Non-contingent electric footshock facilitates the acquisition of intravenous cocaine self-administration in rats. Psychopharmacology (Berl) 1994 Feb;114(1):63–70. doi: 10.1007/BF02245445. [DOI] [PubMed] [Google Scholar]
  14. Goeders N. E., McNulty M. A., Guerin G. F. Effects of alprazolam on intravenous cocaine self-administration in rats. Pharmacol Biochem Behav. 1993 Feb;44(2):471–474. doi: 10.1016/0091-3057(93)90493-d. [DOI] [PubMed] [Google Scholar]
  15. 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. 1973 Jul;186(1):18–30. [PubMed] [Google Scholar]
  16. Goldberg S. T., Kelleher R. T. Behavior controlled by scheduled injections of cocaine in squirrel and rhesus monkeys. J Exp Anal Behav. 1976 Jan;25(1):93–104. doi: 10.1901/jeab.1976.25-93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. KELLEHER R. T., GOLLUB L. R. A review of positive conditioned reinforcement. J Exp Anal Behav. 1962 Oct;5:543–597. doi: 10.1901/jeab.1962.5-s543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lau Chyan E., Sun Lei. The pharmacokinetic determinants of the frequency and pattern of intravenous cocaine self-administration in rats by pharmacokinetic modeling. Drug Metab Dispos. 2002 Mar;30(3):254–261. doi: 10.1124/dmd.30.3.254. [DOI] [PubMed] [Google Scholar]
  19. Lynch W. J., Carroll M. E. Regulation of drug intake. Exp Clin Psychopharmacol. 2001 May;9(2):131–143. doi: 10.1037//1064-1297.9.2.131. [DOI] [PubMed] [Google Scholar]
  20. Lynch W. J., LaBounty L. P., Carroll M. E. A novel paradigm to investigate regulation of drug intake in rats self-administering cocaine or heroin intravenously. Exp Clin Psychopharmacol. 1998 Feb;6(1):22–31. doi: 10.1037//1064-1297.6.1.22. [DOI] [PubMed] [Google Scholar]
  21. Markou A., Weiss F., Gold L. H., Caine S. B., Schulteis G., Koob G. F. Animal models of drug craving. Psychopharmacology (Berl) 1993;112(2-3):163–182. doi: 10.1007/BF02244907. [DOI] [PubMed] [Google Scholar]
  22. Nicola S. M., Deadwyler S. A. Firing rate of nucleus accumbens neurons is dopamine-dependent and reflects the timing of cocaine-seeking behavior in rats on a progressive ratio schedule of reinforcement. J Neurosci. 2000 Jul 15;20(14):5526–5537. doi: 10.1523/JNEUROSCI.20-14-05526.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Norman A. B., Norman M. K., Hall J. F., Tsibulsky V. L. Priming threshold: a novel quantitative measure of the reinstatement of cocaine self-administration. Brain Res. 1999 Jun 12;831(1-2):165–174. doi: 10.1016/s0006-8993(99)01423-7. [DOI] [PubMed] [Google Scholar]
  24. O'Brien C. P., Childress A. R., McLellan T., Ehrman R. Integrating systemic cue exposure with standard treatment in recovering drug dependent patients. Addict Behav. 1990;15(4):355–365. doi: 10.1016/0306-4603(90)90045-y. [DOI] [PubMed] [Google Scholar]
  25. Panlilio L. V., Goldberg S. R., Gilman J. P., Jufer R., Cone E. J., Schindler C. W. Effects of delivery rate and non-contingent infusion of cocaine on cocaine self-administration in rhesus monkeys. Psychopharmacology (Berl) 1998 Jun;137(3):253–258. doi: 10.1007/s002130050618. [DOI] [PubMed] [Google Scholar]
  26. Panlilio L. V., Weiss S. J., Schindler C. W. Cocaine self-administration increased by compounding discriminative stimuli. Psychopharmacology (Berl) 1996 Jun;125(3):202–208. doi: 10.1007/BF02247329. [DOI] [PubMed] [Google Scholar]
  27. Panlilio L. V., Weiss S. J., Schindler C. W. Effects of compounding drug-related stimuli: escalation of heroin self-administration. J Exp Anal Behav. 2000 Mar;73(2):211–224. doi: 10.1901/jeab.2000.73-211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pert A. Neurobiological mechanisms underlying the acquisition and expression of incentive motivation by cocaine-associated stimuli: relationship to craving. NIDA Res Monogr. 1994;145:163–190. [PubMed] [Google Scholar]
  29. Pettit H. O., Justice J. B., Jr Dopamine in the nucleus accumbens during cocaine self-administration as studied by in vivo microdialysis. Pharmacol Biochem Behav. 1989 Dec;34(4):899–904. doi: 10.1016/0091-3057(89)90291-8. [DOI] [PubMed] [Google Scholar]
  30. Pettit H. O., Justice J. B., Jr Effect of dose on cocaine self-administration behavior and dopamine levels in the nucleus accumbens. Brain Res. 1991 Jan 18;539(1):94–102. doi: 10.1016/0006-8993(91)90690-w. [DOI] [PubMed] [Google Scholar]
  31. Pickens R., Thompson T. Cocaine-reinforced behavior in rats: effects of reinforcement magnitude and fixed-ratio size. J Pharmacol Exp Ther. 1968 May;161(1):122–129. [PubMed] [Google Scholar]
  32. Rescorla R. A., Solomon R. L. Two-process learning theory: Relationships between Pavlovian conditioning and instrumental learning. Psychol Rev. 1967 May;74(3):151–182. doi: 10.1037/h0024475. [DOI] [PubMed] [Google Scholar]
  33. Robinson T. E., Berridge K. C. The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev. 1993 Sep-Dec;18(3):247–291. doi: 10.1016/0165-0173(93)90013-p. [DOI] [PubMed] [Google Scholar]
  34. Schindler Charles W., Panlilio Leigh V., Goldberg Steven R. Second-order schedules of drug self-administration in animals. Psychopharmacology (Berl) 2002 Aug 8;163(3-4):327–344. doi: 10.1007/s00213-002-1157-4. [DOI] [PubMed] [Google Scholar]
  35. Shoaib M., Swanner L. S., Beyer C. E., Goldberg S. R., Schindler C. W. The GABAB agonist baclofen modifies cocaine self-administration in rats. Behav Pharmacol. 1998 May;9(3):195–206. [PubMed] [Google Scholar]
  36. Shulman G. D. Experience with the cocaine trigger inventory. Adv Alcohol Subst Abuse. 1989;8(2):71–85. doi: 10.1300/J251v08n02_04. [DOI] [PubMed] [Google Scholar]
  37. Tsibulsky V. L., Norman A. B. Satiety threshold: a quantitative model of maintained cocaine self-administration. Brain Res. 1999 Aug 21;839(1):85–93. doi: 10.1016/s0006-8993(99)01717-5. [DOI] [PubMed] [Google Scholar]
  38. WEISS S. J. SUMMATION OF RESPONSE STRENGTHS INSTRUMENTALLY CONDITIONED TO STIMULI IN DIFFERENT SENSORY MODALITIES. J Exp Psychol. 1964 Aug;68:151–155. doi: 10.1037/h0049180. [DOI] [PubMed] [Google Scholar]
  39. Wallace B. C. Psychological and environmental determinants of relapse in crack cocaine smokers. J Subst Abuse Treat. 1989;6(2):95–106. doi: 10.1016/0740-5472(89)90036-6. [DOI] [PubMed] [Google Scholar]
  40. Weiss S. J. An effective and economical sound-attenuation chamber. J Exp Anal Behav. 1970 Jan;13(1):37–39. doi: 10.1901/jeab.1970.13-37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Weiss S. J. Discriminated response and incentive processes in operant conditioning: a two-factor model of stimulus control. J Exp Anal Behav. 1978 Nov;30(3):361–381. doi: 10.1901/jeab.1978.30-361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Weiss S. J. Discrimination training and stimulus compounding: consideration of non-reinforcement and response differentiation consequences of S. J Exp Anal Behav. 1971 May;15(3):387–402. doi: 10.1901/jeab.1971.15-387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Weiss S. J., Panlilio L. V. Blocking a selective association in pigeons. J Exp Anal Behav. 1999 Jan;71(1):13–24. doi: 10.1901/jeab.1999.71-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Weiss S. J., Panlilio L. V., Schindler C. W. Selective associations produced solely with appetitive contingencies: the stimulus-reinforcer interaction revisited. J Exp Anal Behav. 1993 Mar;59(2):309–322. doi: 10.1901/jeab.1993.59-309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Weiss S. J., Panlilio L. V., Schindler C. W. Single-incentive selective associations produced solely as a function of compound-stimulus conditioning context. J Exp Psychol Anim Behav Process. 1993 Jul;19(3):284–294. [PubMed] [Google Scholar]
  46. Weiss S. J. Stimulus compounding in free-operant and classical conditioning. A review and analysis. Psychol Bull. 1972 Sep;78(3):189–208. doi: 10.1037/h0032956. [DOI] [PubMed] [Google Scholar]
  47. Weiss S. J., Thomas D. A., Weissman R. D. Combining operant-baseline-derived conditioned excitors and inhibitors from the same and different incentive classes: an investigation of appetitive-aversive interactions. Q J Exp Psychol B. 1996 Nov;49(4):357–381. doi: 10.1080/713932635. [DOI] [PubMed] [Google Scholar]
  48. Weissenborn R., Yackey M., Koob G. F., Weiss F. Measures of cocaine-seeking behavior using a multiple schedule of food and drug self-administration in rats. Drug Alcohol Depend. 1995 Jun;38(3):237–246. doi: 10.1016/0376-8716(95)01107-a. [DOI] [PubMed] [Google Scholar]
  49. Wise R. A., Newton P., Leeb K., Burnette B., Pocock D., Justice J. B., Jr Fluctuations in nucleus accumbens dopamine concentration during intravenous cocaine self-administration in rats. Psychopharmacology (Berl) 1995 Jul;120(1):10–20. doi: 10.1007/BF02246140. [DOI] [PubMed] [Google Scholar]

Articles from Journal of the Experimental Analysis of Behavior are provided here courtesy of Society for the Experimental Analysis of Behavior

RESOURCES