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Reinstatement of cocaine-reinforced responding in the rat


Non-contingent “priming” drug injections and conditioned stimuli associated with drug injections led to reinstatement of responding after a period of extinction. Rats implanted with intravenous catheters were trained to self-administer cocaine (1 mg/kg/injection), and then given daily test sessions consisting of a period of self-administration followed by extinction conditions. Test drug injections or conditioned stimuli were presented during extinction and the latency to the first response and the total number of responses following the treatment were measured. Cocaine injections of 0.5, 1.0, and 2.0 mg/kg restored responding during extinction, regardless of the duration of the extinction period (between 10 min and 180 min) since drug self-administration. Amphetamine, apomorphine, and morphine but not ethanol, heroin, or methohexital reinstated previously cocaine-reinforced responding. Amphetamine, cocaine, and morphine did not increase responding in animals trained to bar press only for food reinforcement, suggesting that the reinstatement effect is specific to drug-reinforced responses. The final experiment showed that a tone that had been paired with drug infusions acquired a statistically significant tendency to facilitate responding when tested during extinction but this effect disappeared after the first test presentation of the tone.

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  1. Ando K, Yanagita T (1978) The discriminative stimulus properties of intravenously administered cocaine in rhesus monkeys. In: Colpaert RC, Rosecrans SA (eds) Stimulus properties of drugs: ten years of progress. Elsevier/North Holland, Amsterdam

  2. Anonymous (1939) Alcoholics Anonymous. Works Publishing, New York

  3. Bindra D (1974) A motivational view of learning, performance, and behavior modification. Psychol Rev 81:199–213

  4. Brown ZW, Amit Z, Weeks JR (1976) Simple flow-thru swivel for infusions into unrestrained animals. Pharmacol Biochem Behav 5:363–365

  5. Carr LA, Moore KE (1969) Norepinephrine release from the brain by d-amphetamine in vivo. Science 164:322–323

  6. Collins RJ, Weeks JR, Good PI (1978) Evaluation of the reinforcing properties of psychoactive drugs using rats. Problems of Drug Dependence Proceedings of the 40 Annual Scientific Meeting of the Committee on Problems of Drug Dependence (unpublished)

  7. Colpaert FC, Niemegeers CJE, Janssen PAJ (1979) Discriminative stimulus properties of cocaine: Neuropharmacological characteristics as derived from stimulus generalization experiments. Pharmacol Biochem Behav 10:535–546

  8. Colpaert FC, Rosecrans JA (eds) 1978) Stimulus properties of drugs: ten years of progress, Elsevier/North Holland, Amsterdam

  9. Colpaert FC, Van Bever WFM, Leysen JEMF (1976) Apomorphine: chemistry pharmacology, biochemistry. Int Rev Neurobiol 19:225–268

  10. Davis WM, Smith SG (1976) Role of conditioned reinforcers in the initiation maintenance and extinction of drug-seeking behavior. Pavlov J Biol Sci 11:222–236

  11. Eikelboom R, Stewart J (1979) Conditioned temperature effects using morphine as the unconditioned stimulus. Psychopharmacology 61:31–38

  12. Gerber GJ, Stretch R (1975) Drug-induced reinstatement of extinguished self-administration behavior in monkeys. Pharmacol Biochem Behav 3:1055–1061

  13. Glowinski J, Baldessarini RJ (1966) Norepinephrine metabolism in the brain. Pharmacol Rev 18:1201–1238

  14. Goodman LS, Gilman A (1975) The pharmacological basis of therapeutics. (5th edn), Macmillan, New York

  15. Griffiths RR, Brady RV, Bradford LD (1979) Predicting the abuse liability of drugs with animal drug self-administration procedures: Psychomotor stimulants and hallucinogens. In: Thompson T, Dews PB (eds) Advances in behavioral pharmacology, Vol 2. Academic Press, New York

  16. Hill RT (1970) Facilitation of conditioned reinforcement as a mechanism of psychomotor stimulation. In: Costa E, Garattini S (eds) Amphetamines and related compounds. Raven Press, New York, pp 781–795

  17. Ho BT, Silverman PB (1978) Stimulants as discriminative stimuli. In: Colpaert FC, Rosecrans JA (eds) Stimulus properties of drugs: ten years of progress, Elsevier/North Holland, Amsterdam, pp 53–69

  18. Hodgson R, Rankin H, Stockwell T (1979) Alcohol dependence and the priming effect. Behav Res Ther 17:379–387

  19. Holtzman SG (1976) Stimulation of locomotor activity in the rat by morphine: effects of naloxone and tolerance. Fed Proc 35:265

  20. Joyce EM, Iverson SD (1979) The effect of morphine applied locally to mesencephalic dopamine cell bodies on spontaneous motor activity in the rat. Neurosci Lett 14:207–212

  21. Kumar R, Mitchell F, Stolerman IP (1971) Disturbed patterns of behavior in morphine tolerant and abstinent rats. Br J Pharmacol 42:473–484

  22. Lal H (1977) Drug-induced discriminable stimuli: Past research and future perspectives. In: H Lal (ed) Discriminative stimulus properties of drugs. Plenum Press, New York, pp 207–233

  23. Martin WR, Fraser HF (1961) A comparative study of physiological and subjective effects of heroin and morphine administered intravenously in post-addicts. J Pharmacol Exp Ther 133:338–399

  24. Meyer RE, Mirin SM (1979) The heroin stimulus: Implications for a theory of addiction. Plenum Medical Book Company, New York

  25. O'Brien CP (1976) Experimental analysis of conditioning factors in human narcotic addiction. Pharmacol Rev 27:533–543

  26. Oka T, Hosoya E (1976) Effects of humoral modulators and naloxone on morphine-induced changes in the spontaneous locomotor activity of the rat. Psychopharmacology 47:243–248

  27. Pickens R, Harris WC (1968) Self-administration of d-amphetamine by rats. Psychopharmacologia 12:158–163

  28. Pickens R, Muchow D, De Noble V (1981) Methohexital-reinforced responding in rats: effects of fixed ratio size and injection dose. J Pharmacol Exp Ther 216:205–209

  29. Pickens R, Thompson T (1975) Intravenous preparations for self-administration of drugs by animals. Am Psychol 30:274–276

  30. Randrup A, Munkvad I (1966) Role of catecholamines in the amphetamine excitatory response. Nature 211:540

  31. Rawat AK (1976) Neurochemical consequences of ethanol on the nervous system. In: Pfeiffer CC, Smythies JR (eds) International review of neurobiology, Vol 19. Academic Press, New York, pp 124–172

  32. Ross RB, Renyi AL (1967) Inhibition of the uptake of tritiated catecholamines by anti-depressants and related compounds. Eur J Pharmacol 2:181–186

  33. Sideroff SI, Jarvik ME (1977) Conditioned responses to a video tape showing heroin related stimuli. Proceedings of the Second Annual National Conference on Drug Abuse, San Francisco, California (unpublished)

  34. Silverman PB, Ho BT (1977) Characterization of discriminative response control by psychomotor stimulants. In: Lal H (ed) Discriminative stimulus properties of drugs. Plenum Press, New York, pp 107–119

  35. Smith SG, Werner TE, Davis WM (1975) Intravenous drug self-administration in rats: Substitution of ethyl alcohol for morphine. Psychol Red 25:17–20

  36. Sobell MB, Sobell LC (1978) Behavioral treatment of alcohol problems: Individualized therapy and controlled drinking. Plenum Press, New York

  37. Spealman RD, Goldberg SR (1978) Drug self-administration by laboratory animals: Control by schedules of reinforcement. Ann Rev Pharmacol Toxicol 18:313–339

  38. Stretch R, Gerber GJ (1973) Drug-induced reinstatement of amphetamine self-administration behavior in monkeys. Can J Psychol 27:168–177

  39. van Ree JM, de Wied D (1977) Heroin self-administration is under control of vasopressin. Life Sci 21:315–320

  40. Wikler A (1965) In: Wilner DM, Kassebaum GG (eds) Conditioning factors in opiate addiction and relapse, McGraw Hill, New York, pp 85–100

  41. Yokel RA, Pickens R (1974) Drug level of d- and l-amphetamine during intravenous self-administration. Psychopharmacologia 34:255–264

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Correspondence to Jane Stewart.

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de Wit, H., Stewart, J. Reinstatement of cocaine-reinforced responding in the rat. Psychopharmacology 75, 134–143 (1981).

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Key words

  • Cocaine self-administration
  • Reinstatement
  • Priming
  • Conditioned drug effects