, Volume 116, Issue 2, pp 217–225 | Cite as

Individual differences in behavior following amphetamine, GBR-12909, or apomorphine but not SKF-38393 or quinpirole

  • M. Stacy Hooks
  • Declan N. C. Jones
  • Stephen G. Holtzman
  • Jorge L. Juncos
  • Peter W. Kalivas
  • Joseph B. JusticeJr


Subjects that respond more to a novel environment show a greater locomotor response to drugs of abuse such as cocaine and amphetamine. The current study was performed to examine differences between high (HR) and low (LR) responding rats to a novel environment following administration of amphetamine, a selective dopamine uptake blocker (GBR-12909), a nonselective dopamine agonist (apomorphine), and selective dopamine D1 and D2/D3 agonists. A behavioral checklist and a rating scale were used to determine the behavioral arousal caused by administration of amphetamine (0, 0.5, 2.0, and 8.0 mg/kg), GBR-12909 (0, 1.25, 5.0, and 20.0 mg/kg), apomorphine (0, 0.1, 0.3, and 1 mg/kg), SKF 38393 (0, 2.5, 10, and 40 mg/kg), or quinpirole (0, 0.05, 0.5, and 5.0 mg/kg). The five drugs produced behavioral activation profiles distinct from each other. Following amphetamine administration, both HR and LR subjects showed dose dependent increases in behavioral arousal. The behaviors primarily affected were sniffing, locomotor activity, rearing, and oral activity. HR rats showed a greater overall behavioral response to amphetamine administration compared with LR rats and there were differences in specific behaviors between the two groups. Following GBR-12909 administration, all subjects showed dose dependent increases in sniffing, locomotor activity, and rearing. Differences between HR and LR were observed in sniffing, locomotor activity, and rearing behaviors. HR and LR both showed dose dependent increases in behavior following apomorphine administration. HR showed greater behavioral activation after apomorphine than LR. SKF 38393 produced pronounced increases in the amount of sniffing, grooming, and intense grooming, in addition to increasing the overall behavioral rating of all subjects, while quinpirole produced increases in sniffing, locomotor activity, and oral movements. However, the behavioral effects of SKF 38393 and quinpirole did not differ between HR and LR. These results suggest that activation of the dopamine system but probably not only one type of dopamine receptor is sufficient to produce behavioral differences between high and low responding subjects.

Key words

Individual differences Novelty Amphetamine Apomorphine SKF 38393 Quinpirole Dopamine receptors GBR-12909 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bradberry CW, Gruen RJ, Berridge CW, Roth RH (1991) Individual differences in behavioral measures: correlations with nucleus accumbens dopamine by microdialysis. Pharmacol Biochem Behav 39:877–882Google Scholar
  2. Creese I, Iversen SD (1973) Blockage of amphetamine-induced motor stimulation and stereotypy in the adult rat following neonatal treatment with 6-hydroxydopamine. Brain Res 55:369–382Google Scholar
  3. Farfel GM, Kleven MS, Woolverton WL, Seiden LS, Perry BD (1992) Effects of repeated injections of cocaine on catecholamine receptor binding sites, dopamine transporter binding sites and behavior in rhesus monkey. Brain Res 578:235–243Google Scholar
  4. Fray PJ, Sahakian BJ, Robbins TW, Koob GF, Iversen SD (1980) An observational method for quantifying the behavioural effects of dopamine agonist: contrasting effects ofd-amphetamine and apomorphine. Psychopharmacology 69:253–259Google Scholar
  5. Goeders NE, Kuhar MJ (1987) Chronic cocaine administration induces opposite changes in dopamine receptors in the striatum and nucleus accumbens. Alcohol Drug Res 7:207–216Google Scholar
  6. Heikkila RE, Manzino L (1984) Behavioral properties of GBR 12909, GBR 13069 and GBR 13098; specific inhibitors of dopamine uptake. Eur J Pharmacol 103:241–248Google Scholar
  7. Hooks MS, Jones GH, Smith AD, Justice JB Jr (1991a) Individual differences in locomotor activity and sensitization. Pharmacol Biochem Behav 38:467–470Google Scholar
  8. Hooks MS, Jones GH, Smith AD, Neill DB, Justice JB Jr (1991b) Response to novelty predicts the locomotor and nucleus accumbens dopamine response to cocaine. Synapse 9:121–128Google Scholar
  9. Hooks MS, Jones GH, Neill DB, Justice JB Jr (1992a) Individual differences in amphetamine sensitization: dose-dependent effects. Pharmacol Biochem Behav 41:203–210Google Scholar
  10. Hooks MS, Colvin AC, Juncos JL, Justice JB Jr (1992b) Individual differences in basal and cocaine stimulated extracellular dopamine in the nucleus accumbens using quantitative microdialysis. Brain Res 587:306–312Google Scholar
  11. Hooks MS, Jones GH, Liem BJ, Justice JB Jr (1992c) Sensitization and individual differences to IP amphetamine, cocaine, or caffeine following repeated intra-cranial amphetamine infusions. Pharmacol Biochem Behav 43:815–823Google Scholar
  12. Hooks MS, Juncos JL, Justice JB Jr, Kalivas PW (1993) The relationship between vulnerability to drug abuse and components of the dopamine system. J Neurosci (submitted)Google Scholar
  13. 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 167:385–395Google Scholar
  14. Kelly PH, Iversen SD (1976) Selective 6-OHDA-induced destruction of mesolimbic dopamine neurons: abolition of psychostimulant-induced locomotor activity in rats. Eur J Pharmacol 40:45–56Google Scholar
  15. Kleven MS, Perry BD, Woolverton WL, Seiden LS (1990) Effects of repeated injections of cocaine on D1 and D2 dopamine receptors in rat brain. Brain Res 532:265–270Google Scholar
  16. Kullback S (1968) Information theory and statistics. Dover, New YorkGoogle Scholar
  17. Miserendino MJD, Kosten TA, Guitart X, Chi S, Nestler EJ (1992) Individual differences in vulnerability to drug-addiction: behavioral and biochemical correlates. Soc Neurosci Abstr 18:450.12Google Scholar
  18. Molloy AG, Waddington JL (1987) Assessment of grooming and other behavioural responses to the D-1 dopamine receptor agonist SKF 38393 and itsR- andS-enantiomers in the intact adult rat. Psychopharmacology 92:164–168Google Scholar
  19. Nielsen EB, Nielsen M, Braestrup C (1983) Reduction of3H-spiroperidol binding in rat striatum and frontal cortex by chronic amphetamine: dose-response, time course and role of sustained dopamine release. Psychopharmacology 81:81–85Google Scholar
  20. Piazza PV, Deminiere JM, LeMoal M, Simon H (1989) Factors that predict individual vulnerability to amphetamine self-administration. Science 29:1511–1513Google Scholar
  21. Piazza PV, Rouge-Pont F, Deminiere JM, Kharoubi M, LeMoal M Simon H (1991) Dopaminergic activity is reduced in the prefrontal cortex and increased in the nucleus accumbens of rats predisposed to develop amphetamine self-administration. Brain Res 567:169–174Google Scholar
  22. Robbins TW (1977) A critique of the methods available for the measurement of spontaneous motor activity. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol. 7. Plenum, New York, pp 37–82Google Scholar
  23. Segal DS (1975) Behavioral and neurochemical correlates of repeatedd-amphetamine administration. In: Mandell AJ (ed) Advances in biochemical psychopharmacology, vol. 13. Raven Press, New York, pp 247–266Google Scholar
  24. Sharp T, Kingston J, Grahame-Smith DG (1990) Repeated ECS enhances dopamine D-1 but not D-2 agonist-induced behavioural responses in rats. Psychopharmacology 100:110–114Google Scholar
  25. Ujike H, Akiyama K, Otsuki S (1990) D-2 but not D-1 dopamine agonists produce augmented behavioral response in rats after subchronic treatment with methamphetamine or cocaine. Psychopharmacology 102:459–464Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • M. Stacy Hooks
    • 1
  • Declan N. C. Jones
    • 2
  • Stephen G. Holtzman
    • 2
  • Jorge L. Juncos
    • 3
  • Peter W. Kalivas
    • 1
  • Joseph B. JusticeJr
    • 4
  1. 1.Alcohol and Drug Abuse Program, Department of Veterinary and Comparative Anatomy, Pharmacology, and PhysiologyWashington State University, PullmanWashingtonUSA
  2. 2.Department of PharmacologyEmory UniversityAtlantaUSA
  3. 3.Department of NeurologyEmory UniversityAtlantaUSA
  4. 4.Department of ChemistryEmory UniversityAtlantaUSA

Personalised recommendations