, Volume 105, Issue 4, pp 501–507 | Cite as

Effects of selective D1 and D2 dopamine antagonists on the development of behavioral sensitization to apomorphine

  • Bruce A. Mattingly
  • James K. Rowlett
  • Jamison T. Graff
  • Billie Jo Hatton
Original Investigations


The objective of the present study was to determine whether the development of behavioral sensitization to apomorphine could be blocked by either D1 or D2 selective dopamine antagonists. In three experiments, male rats received 10–21 daily injections of a selective D1 (SCH 23390; 0 or 0.5 mg/kg IP) or D2 (sulpiride; 0, 30, or 100 mg/kg IP) antagonist followed by an apomorphine (0 or 1.0 mg/kg SC) injection. In two experiments, the rats were tested for locomotor activity in photocell arenas after the daily injections. In all experiments, the rats were tested for sensitization to apomorphine following the training phase. The results indicated that apomorphine produced a progressively greater increase in locomotor activity with each injection, and this apomorphine-induced increase in activity was completely blocked by both sulpiride and SCH 23390 treatments. However, although both sulpiride and SCH 23390 blocked apomorphine-induced activity, only SCH 23390 injections prevented the development of sensitization to apomorphine. That is, rats pretreated with sulpiride and apomorphine displayed significant sensitization when subsequently tested with a challenge dose of apomorphine alone. These findings suggest that the development of behavioral sensitization to apomorphine is related specifically to the stimulation of dopamine D1 receptors.

Key words

Behavioral sensitization Apomorphine Sulpiride SCH 23390 Locomotor activity 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ackerman JM, White FJ (1989) A10 dopamine somatodendritic autoreceptor sensitivity following withdrawal from repeated cocaine treatment. Neurosci Lett 117:181–187CrossRefGoogle Scholar
  2. Amalric M, Koob GF, Creese I, Swerdlow NR (1986) “Selective” D-1 and D-2 receptor antagonists fail to differentially alter supersensitive locomotor behavior in the rat. Life Sci 39:1985–1993CrossRefPubMedGoogle Scholar
  3. Bergman J, Kamien JB, Spealman RD (1990) Antagonism of cocaine self-administration by selective dopamine D1 and D2 antagonists. Behav Pharmacol 1:355–363PubMedGoogle Scholar
  4. Braun AR, Chase TN (1988) Behavioral effects of chronic exposure to selective D-1 and D-2 dopamine receptor agonists. Eur J Pharmacol 147:441–451CrossRefPubMedGoogle Scholar
  5. Breese GR, Creese I (1986) Neurobiology of central D1-dopamine receptors. Plenum Press, New YorkGoogle Scholar
  6. Carlson JH, Bergstrom DA, Walters JR (1987) Stimulation of both D1 and D2 dopamine receptors appears necessary for full expression of postsynaptic effects of dopamine agonists: a neurophysiological study. Brain Res 400:205–218CrossRefPubMedGoogle Scholar
  7. Castro R, Abreu P, Calzadilla CH, Rodriquez M (1985) Increased or decreased locomotor response in rats following repeated administration of apomorphine depends on dosage interval. Psychopharmacology 85:333–339CrossRefPubMedGoogle Scholar
  8. Clark D, White FJ (1987) Review: D1 dopamine receptor — the search for a function: a critical evaluation of the D1/D2 dopamine receptor classification and its functional implications. Synapse 1:347–388CrossRefPubMedGoogle Scholar
  9. Criswell H, Mueller RA, Breese GR (1989) Priming of D1-dopamine responses: long-lasting behavioral supersensitivity to a D1-dopamine agonist following repeated administration to 6-OHDA-lesioned rats. J Neurosci 9:125–133PubMedGoogle Scholar
  10. Gold LH, Swerdlow NR, Koob GF (1988) The role of mesolimbic dopamine in conditioned locomotion produced by amphetamine. Behav Neurosci 102:544–552CrossRefPubMedGoogle Scholar
  11. Henry DJ, White FJ (1989) Effects of repeated cocaine administration on the sensitivity of D1 and D2 receptors in the nucleus accumbens: electrophysiological studies. Soc Neurosci Abstr 15:1010Google Scholar
  12. Kalivas PW, Duffy P (1990) Effect of acute and daily cocaine treatment on extracellular dopamine in the nucleus accumbens. Synapse 5:48–58CrossRefPubMedGoogle Scholar
  13. Kalivas PW, Weber B (1988) Amphetamine injection into the ventral mesencephalon sensitizes rats to peripheral amphetamine and cocaine. J Pharmacol Exp Ther 245:1095–1101PubMedGoogle Scholar
  14. Kuczenski R, Leith NJ (1981) Chronic amphetamine: is dopamine a link in or a mediator of the development of tolerance and reverse tolerance? Pharmacol Biochem Behav 15:405–413CrossRefPubMedGoogle Scholar
  15. Kuczenski R, Segal DS (1988) Psychomotor stimulant-induced sensitization: behavioral and neurochemical correlates. In: Kalivas PW, Barnes CD (eds) Sensitization in the nervous system. Telford Press, New JerseyGoogle Scholar
  16. Kuczenski R, Segal DS (1989) Concomitant characterization of behavioral and striatal neurotransmitter response to amphetamine using in vivo microdialysis. J Neurosci 9:2051–2065PubMedGoogle Scholar
  17. Lappalainen J, Hietala J, Sjoholm B, Syvalahti E (1990) Effects of chronic SCH 23390 treatment on dopamine autoreceptor function in rat brain. Eur J Pharmacol 179:315–321CrossRefPubMedGoogle Scholar
  18. Levy AD, Kim JJ, Ellison GD (1988) Chronic amphetamine alters D-2 but not D-1 agonist-induced behavioral responses in rats. Life Sci 43:1207–1213CrossRefPubMedGoogle Scholar
  19. Mattingly BA, Gotsick JE (1989) Conditioning and experiential factors affecting the development of sensitization to apomorphine. Behav Neurosci 103:1311–1317CrossRefPubMedGoogle Scholar
  20. Mattingly BA, Rowlett JK (1989) Effects of repeated apomorphine and haloperidol treatments on subsequent sensitivity to apomorphine. Pharmacol Biochem Behav 34:345–347CrossRefPubMedGoogle Scholar
  21. Mattingly BA, Gotsick JE, Marin C (1988a) Locomotor activity and stereotypy in rats following repeated apomorphine treatments at 1-, 3-, or 7-day intervals. Pharmacol Biochem Behav 31:871–875CrossRefPubMedGoogle Scholar
  22. Mattingly BA, Gotsick JE, Salamanca K (1988b) Latent sensitization to apomorphine following repeated low doses. Behav Neurosci 102:553–558CrossRefPubMedGoogle Scholar
  23. Moore NA, Axton MS (1990) The role of multiple dopamine receptors in apomorphine and N-n-propylnorapomorphine-induced climbing and hypothermia. Eur J Pharmacol 178:195–201CrossRefPubMedGoogle Scholar
  24. Peris J, Zahniser NR (1989) Persistent augmented dopamine release after acute cocaine requires dopamine receptor activation. Pharmacol Biochem Behav 32:71–76CrossRefPubMedGoogle Scholar
  25. Plaznik A, Stefanski R, Kostowski W (1989) Interaction between accumbens D1 and D2 receptors regulating rat locomotor activity. Psychopharmacology 99:558–562CrossRefPubMedGoogle Scholar
  26. Robinson TE, Becker JB (1986) Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis. Brain Res Rev 11:157–198CrossRefGoogle Scholar
  27. Robinson TE, Jurson PA, Bennett JA, Bentgen KM (1988) Persistent sensitization of dopamine neurotransmission in ventral striatum (nucleus accumbens) produced by prior experience with (+)-amphetamine: a microdialysis study in freely moving rats. Brain Res 462:211–222CrossRefPubMedGoogle Scholar
  28. Ross SB, Jackson DM, Edwards SR (1989) The involvement of dopamine D1 and D2 receptors in the locomotor stimulation produced by (+)-amphetamine in naive and dopamine-depleted mice. Pharmacol Toxicol 64:72–77PubMedGoogle Scholar
  29. Rowlett JK, Mattingly BA, Bardo MT (1991) Neurochemical and behavioral effects of acute and chronic treatment with apomorphine in rats. Neuropharmacology 30:191–197CrossRefPubMedGoogle Scholar
  30. Stewart J, Vezina P (1989) Microinjections of Sch-23390 into the ventral tegmental area and substantia nigra pars reticulata attenuate the development of sensitization to the locomotor activating effects of systemic amphetamine. Brain Res 495:401–416CrossRefPubMedGoogle Scholar
  31. Ujike H, Onoune T, Akiyama K, Hamamura T, Otsuki S (1989) Effects of selective D-1 and D-2 dopamine antagonists on the development of methamphetamine-induced behavioral sensitization. Psychopharmacology 98:89–92CrossRefPubMedGoogle Scholar
  32. Vaughn DM, Severson JA, Woodward JJ, Randall PK, Riffee WH, Leslie SW, Wilcox RE (1990) Behavioral sensitization following subchronic apomorphine treatment — possible neurochemical basis. Brain Res 526:37–44CrossRefPubMedGoogle Scholar
  33. Vezina P, Stewart J (1989) The effect of dopamine receptor blockade on the development of sensitization to the locomotor activating effects of amphetamine and morphine. Brain Res 499:108–120CrossRefPubMedGoogle Scholar
  34. Zahniser NR, Peris J, Dwoskin LP, Curella P, Yasuda RP, O'Keefe L, Boyson SJ (1988) Sensitization to cocaine in the nigrostriatal dopamine system. In: Clovet D, Asghar K, Brown R (eds) National Institute on Drug Abuse Research Monograph #88. US Government Printing Office, Washington DC.Google Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Bruce A. Mattingly
    • 1
  • James K. Rowlett
    • 1
  • Jamison T. Graff
    • 1
  • Billie Jo Hatton
    • 1
  1. 1.Department of PsychologyMorehead State UniversityMoreheadUSA

Personalised recommendations