, Volume 111, Issue 2, pp 202–206 | Cite as

Self-administration of GBR 12909 on a fixed ratio and progressive ratio schedule in rats

  • David C. S. Roberts
Original Investigations


Intravenous self-administration of GBR 12909, an indirect dopamine agonist, was examined on a Fixed Ratio (FR 1) and a Progressive Ratio (PR) schedule of reinforcement in rats. Subjects were first trained to self-administer cocaine (1.5 mg/kg/inj) during daily 5 h sessions, after which GBR 12909 (0.187–1.5 mg/kg/inj) was substituted. On the FR 1 schedule, the inter-infusion interval for GBR 12909 self-administration was directly related to dose and was approximately three times longer than that established for equivalent doses of cocaine. Breaking points on the PR schedule were comparable for GBR 12909 and cocaine self-administration. The data indicate that, compared to cocaine, GBR 12909 has a longer duration of action and a similar reinforcing efficacy.

Key words

GBR 12909 Cocaine Self-administration Progressive ratio schedule Fixed ratio Rats 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anderson PH (1989) The dopamine uptake inhibitor GBR 12909: selectivity and molecular mechanism of action. Eur J Pharmacol 166:493–504CrossRefPubMedGoogle Scholar
  2. Baldo BA, Kelley AE (1991) Cross-sensitization between cocaine and GBR 12909, a dopamine uptake inhibitor. Brain Res Bull 27:105–108CrossRefPubMedGoogle Scholar
  3. Bedford JA, Bailey LP, Wilson MC (1978) Cocaine reinforced progressive ratio performance in the rhesus monkey. Pharmacol Biochem Behav 9:631–638CrossRefPubMedGoogle Scholar
  4. Bergman J, Madras BK, Johnson SE, Spealman RD (1989) Effects of cocaine and related drugs in nonhuman primates. III. Self-administration by squirrel monkeys. J Pharmacol Exp Ther 251:150–155PubMedGoogle Scholar
  5. Britton DR, Curzon P, MacKenzie RG, Kebabian JW, Williams JEG, Kerkman D (1991) Evidence for involvement of both D1 and D2 receptors in maintaining cocaine self-administration. Pharmacol Biochem Behav 39:911–915CrossRefPubMedGoogle Scholar
  6. Cunningham KA, Callahan PM (1991) Monoamine reuptake inhibitors enhance the discriminative state induced by cocaine in the rat. Psychopharmacology 104:177–180PubMedGoogle Scholar
  7. Griffiths RR, Findley JD, Brady JV, Gutcher K, Robinson WW (1975) Comparison of progressive-ratio performance maintained by cocaine, methylphenidate and secobarbitol. Psychopharmacology 43:81–83CrossRefGoogle Scholar
  8. Griffiths RR, Brady JV, Snell JD (1978) Progressive-ratio performance maintained by drug infusions: comparison of cocaine, diethylpropion, chlorphentermine, and fenfluramine. Psychopharmacology 56:5–13Google Scholar
  9. Griffiths RR, Bradford LD, Brady JV (1979) Progressive ratio and fixed ratio schedules of cocaine-maintained responding in baboons. Psychopharmacology 65:125–136Google Scholar
  10. Heikkila RE, Manzino L (1984) Behavioral properties of GBR 12909, GBR 13069 and GBR 13098: Specific inhibitors of dopamine uptake. Eur J Pharmacol 103:241–248PubMedGoogle Scholar
  11. Hoffmeister F (1979) Progressive-ratio performance in the rhesus monkey maintained by 3 opiate infusions. Psychopharmacology 62:181–186CrossRefPubMedGoogle Scholar
  12. Howell LL, Byrd LD (1991) Characterization of the effects of cocaine and GBR 12909, a dopamine uptake inhibitor, on behavior in the squirrel monkey. J Pharmacol exp Ther 258:178–185PubMedGoogle Scholar
  13. Kelley AE, Lang CG (1988) A behavioral investigation of GBR 12909: effects on motor activity, fixed interval responding, and conditioned reinforcement. Soc Neurosci Abstr 14:662Google Scholar
  14. Kelley AE, Lang CG (1989) Effects of GBR 12909, a selective dopamine uptake inhibitor, on motor activity and operant behavior in the rat. Eur J Pharmacol 167:385–395CrossRefPubMedGoogle Scholar
  15. Kleven MS, Anthony EW, Nielson EB, Woolverton WL (1988) Reinforcing and discriminative stimulus effects of GBR 12909 in rhesus monkeys. Soc Neurosci Abstr 14:305Google Scholar
  16. Kuhar MJ, Ritz MC, Boja JW (1991) The dopamine hypothesis of the reinforcing properties of cocaine. TINS 14:299–302PubMedGoogle Scholar
  17. Loh EA, Roberts DCS (1990) Break-points on a progressive ratio schedule reinforced by intravenous cocaine increase following depletion of forebrain serotonin. Psychopharmacology 101:262–266PubMedGoogle Scholar
  18. Lyness WH, Friedle NM, Moore KE (1979) Destruction of dopaminergic nerve terminals in nucleus accumbens: effects ofd-amphetamine self-administration. Pharmacol Biochem Behav 11:553–556CrossRefPubMedGoogle Scholar
  19. Melia KF, Spealman RD (1991) Pharmacological characterization of the discriminative-stimulus effects of GBR 12909. J Pharmacol Exp Ther 258:626–632PubMedGoogle Scholar
  20. Meloni R, Gale K (1991) Cocaine-induced turning behavior in rats with 6-hydroxydopamine lesions: effect of transplants of fetal substantia nigra. Eur J Pharmacol 209:113–117CrossRefPubMedGoogle Scholar
  21. Pettit HO, Justice JB Jr (1990) Dopamine in the nucleus accumbens during cocaine self-administration as studied by in vivo microdialysis. Pharmacol Biochem Behav 34:899–904CrossRefGoogle Scholar
  22. Pettit HO, Justice JB Jr (1991) Effect of dose on cocaine self-administration behavior and dopamine levels in the nucleus accumbens. Brain Res 539:94–102CrossRefPubMedGoogle Scholar
  23. Pettit HO, Ettenberg A, Bloom FE, Koob GF (1984) Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin self-administration in rats. Psychopharmacology 84:167–173CrossRefPubMedGoogle Scholar
  24. Risner ME, Cone EJ (1986) Intravenous self-administration of fencamfamine and cocaine by beagle dogs under fixed-ratio and progressive-ratio schedules of reinforcement. Drug Alcohol Depend 17:93–102CrossRefPubMedGoogle Scholar
  25. Risner ME, Goldberg SR (1983) A comparison of nicotine and cocaine self-administration in the dog: fixed ratio and progressive-ratio schedules of intravenous drug infusion. J Pharm Exp Ther 224:319–326Google Scholar
  26. Risner ME, Silcox DL (1981) Psychostimulant self-administration by beagle dogs in a progressive-ratio paradigm. Psychopharmacology 75:25–30CrossRefPubMedGoogle Scholar
  27. Roberts DCS (1989) Breaking points on a progressive ratio schedule reinforced by intravenous apomorphine increase daily following 6-hydroxydopamine lesions of the nucleus accumbens. Pharmacol Biochem Behav 32:43–47CrossRefPubMedGoogle Scholar
  28. Roberts DCS, Goeders N (1989) Drug self-administration: experimental methods and determinants. In: Boulton AA, Baker GB, Greenshaw AJ (eds) Neuromethods, vol 13, Psychopharmacology. Humana Press, New Jersey, pp 349–398Google Scholar
  29. Roberts DCS, Koob GF (1982) Disruption of cocaine self-administration following 6-hydroxydopamine lesions of the ventral tegmental area in rats. Pharmacol Biochem Behav 17:901–904CrossRefPubMedGoogle Scholar
  30. Roberts DCS, Richardson NR (1992) Self-administration of psychomotor stimulants using progressive ratio schedules. In: Wu P, Boulton A, Baker GB (eds) Animal models of drug addiction. Humana, New Jersey, p 1Google Scholar
  31. Roberts DCS, Vickers GJ (1984) Atypical neuroleptics increase self-administration of cocaine: an evaluation of a behavioral screen for antipsychotic drug activity. Psychopharmacology 82:135–139Google Scholar
  32. Roberts DCS, Koob GF, Klonoff P, Fibiger HC (1980) Extinction and recovery of cocaine self-administration following 6-hydroxydopamine lesions of the nucleus accumbens. Pharmacol Biochem Behav 12:781–787CrossRefPubMedGoogle Scholar
  33. Roberts DCS, Loh EA, Vickers GJ (1989) Self-administration of cocaine on a progressive ratio schedule in rats: dose-response relationship and effect of haloperidol pretreatment. Psychopharmacology 97:535–538Google Scholar
  34. Rompré P-P, Bauco P (1990) GBR 12909 reverses the SCH 23390 inhibition of rewarding effects of brain stimulation. Eur J Pharmacol 182:181–184CrossRefPubMedGoogle Scholar
  35. Spyraki C, Fibiger HC (1981) Intravenous self-administration of nomifensine in rats: implications for abuse potential in humans. Science 212:1167–1168PubMedGoogle Scholar
  36. Van der Zee P, Koger HS, Gootjes J, Hespe W (1980) Aryl 1,4-dialk(en)ylpiperazines as selective and very potent inhibitors of dopamine uptake. Eur J Med Chem 15:363–370Google Scholar
  37. Wilson MC, Schuster CR (1976) Mazindol self-administration in the rhesus monkey. Pharmacol Biochem Behav 4:207CrossRefPubMedGoogle Scholar
  38. Witkin JM, Nichols DE, Terry P, Katz JL (1991) Behavioral effects of selective dopaminergic compounds in rats discriminating cocaine injections. J Pharmacol Exp Ther 257:706–713PubMedGoogle Scholar
  39. Woolverton WL (1986) Effects of a D1 and D2 dopamine antagonist on the self-administration of cocaine and piribedil by rhesus monkeys. Pharmacol Biochem Behav 24:531–535CrossRefPubMedGoogle Scholar
  40. Woolverton WL, Virus RM (1989) The effects of a D1 and D2 dopamine antagonist on behavior maintained by cocaine or food. Pharmacol Biochem Behav 32:691–697CrossRefPubMedGoogle Scholar
  41. Yokel RA, Wise RA (1975) Increased lever pressing for amphetamine after pimozide in rats: implication for a dopamine theory of reward. Science 187:547–549PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • David C. S. Roberts
    • 1
  1. 1.Life Sciences Research Building, Department of PsychologyCarleton UniversityOttawaCanada

Personalised recommendations