, Volume 108, Issue 3, pp 256–262 | Cite as

Psychopharmacological responsiveness to the dopamine agonist quinpirole in normal weanlings and in weanling offspring exposed gestationally to cocaine

  • C. A. Moody
  • N. A. Frambes
  • L. P. Spear
Original Investigations


The behavioral responsiveness to challenge doses of the D2 agonist quinpirole was examined in 21-day-old normal offspring (experiment 1) as well as offspring exposed gestationally to cocaine (experiment 2). In both experiments weanling rats received a subcutaneous injection of 0 (0.9% saline), 0.04, 0.08, 0.5, or 1.0 mg/kg/3 cc of the D2 agonist quinpirole and were placed in a divided glass testing apparatus containing either a dish of wet mash plus a food pellet or wood block (experiment 1) or both a food pellet and a wood block (experiment 2). Behaviors were recorded for 5 min via time-sampling at 30 and 60 min post-injection. In experiment 1 the three highest doses of quinpirole increased the amount of forward locomotion, rearing, sniffing and probing, as well as increasing directed oral movements at both the wood block and food pellet; in general these findings are reminiscent of those reported previously in adult animals. In experiment 2, cocaine-exposed weanlings exhibited an increased sensitivity to the stimulating effects of a low dose of the D2 agonist for forward locomotion and rearing as well as an increase in the overall incidence of sniffing behavior and chewing on food pellets. These data provide psychopharmacological evidence that the increase in striatal D2 binding previously observed in weanling offspring exposed gestationally to cocaine (Scalzo et al. 1990) may be associated with an increased behavioral sensitivity to the D2 agonist quinpirole.

Key words

Dopamine Cocaine Prenatal exposure Quinpirole Development 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arnt J, Hyttel J, Perregaard J (1987) Dopamine D-1 receptor agonists combined with the selective D-2 agonist quinpirole facilitate the expression of oral stereotyped behavior in rats. Eur J Pharmacol 133:137–145Google Scholar
  2. Baez LA, Burt DK, Granneman J, Shanklin C (1979) Dopaminergic antagonism and catalepsy in the developing rat. Eur J Pharmacol 54:15–20Google Scholar
  3. Bruinink A, Lichtensteiger W, Schlumpf M (1983) Pre- and postnatal entogeny and characterization of dopaminergic D2, serotonergic S2, and spirodecanone binding sites in rat forebrain. J Neurochem 40:1227–1236Google Scholar
  4. Chasnoff IJ, Burns WJ, Schnoll SH, Burns KA (1985) Cocaine use in pregnancy. N Engl J Med 313:666–669Google Scholar
  5. Chasnoff IJ, Burns KA, Burns WJ (1987) Cocaine use in pregnancy: perinatal morbidity and mortality. Neurotoxicol Teratol 9:291–293Google Scholar
  6. Creese I, Iversen SD (1974) Blockage of amphetamine induced motor stimulation and stereotypy in the adult rat following neonatal treatment with 6-hydroxydopamine. Brain Res 55:369–382Google Scholar
  7. Dall'Olio R, Gandolfi O, Vaccheri A, Roncada P, Montanaro N (1988) Changes in behavioral responses to the combined administration of D1 and D2 dopamine agonists in normosensitive and D1 supersensitive rats. Psychopharmacology 95:381–385Google Scholar
  8. Dow-Edwards DL (1991) Cocaine effects on fetal development: a comparison of clinical and animal research findings. Neurotoxical Teratol 13:347–352Google Scholar
  9. Eilam D, Szechtman H (1989) Biphasic effect of D-2 agonist quinpirole on locomotion and movements. Eur J Pharmacol 161:151–157Google Scholar
  10. Eilam D, Golani I, Szechtman H (1989) D2 agonist quinpirole induces perseveration of routes and hyperactivity but no perseveration of movements. Brain Res 490:255–267Google Scholar
  11. Ellison G, Johansson P, Levin E, See R, Gunne L (1988) Chronic neuroleptics alter the effects of the D1 agonist Sk&f 38393 and the D2 agonist Ly171555 on oral movements in rats. Psychopharmacology 96:253–257Google Scholar
  12. Gelbard HA, Teicher MH, Faedda G, Baldessarini RJ (1989) Postnatal development of dopamine D1 and D2 receptor sites in rat striatum. Brain Res 49:123–130Google Scholar
  13. Hall WG, Williams CL (1983) Suckling isn't feeding, or is it? A search for developmental continuities. Adv Stud Behav 13:219–254Google Scholar
  14. Heyser CJ, Chen WJ, Miller J, Spear NE, Spear LP (1990) Prenatal cocaine exposure induces deficits in Pavlovian conditioning and sensory preconditioning among infant rat pups. Behav Neurosci 104:955–963Google Scholar
  15. Johansson P, Levin E, Gunne L, Ellison G (1987) Opposite effects of a D1 and a D2 agonist on oral movements in rats. Eur J Pharmacol 134:83–88Google Scholar
  16. Joyce EM, Iversen SD (1984) Dissociable effects of 6-OHDA-induced lesions of neostriatum on anorexia, locomotor activity and stereotypy: the role of behavioral competition. Psychopharmacology 83:363–366Google Scholar
  17. Lindvall O, Bjorkland A (1982) Neuroanatomy of central dopamine pathways: review of recent progress. In: Kohsaka M, Shohmori T, Tsukada Y, Woodruff GN (eds) Advances in the biosciences, vol 37. Advances in dopamine research. Pergamon Press, Elmsford, NY, pp 297–311Google Scholar
  18. Martin-Iverson MT, Dourish CT (1988) Role of dopamine D-1 and D-2 receptor subtypes in mediating dopamine agonist effects on food consumption in rats. Psychopharmacology 96:370–374Google Scholar
  19. McDougall SA, Arnold TF, Nonneman AJ (1990) Ontogeny of locomotor activity and grooming in the young rat: role of dopamine D1 and D2 receptors. Eur J Pharmacol 186:223–230Google Scholar
  20. Moody CA, Spear LP (1992) Ontogenetic differences in the psychopharmacological responses to separate and combined stimulation of D1 and D2 dopamine receptors during the neonatal to weanling age period. Psychopharmacology 106:161–168Google Scholar
  21. Pardo JV, Creese I, Burt DR, Snyder SH (1977) Ontogenesis of dopamine receptor binding in the corpus striatum of the rat. Brain Res 125:376–382Google Scholar
  22. Scalzo FM, Ali SF, Frambes NA, Spear LP (1990) Weanling rats exposed prenatally to cocaine exhibit an increase in striatal D2 dopamine binding associated with an increase in ligand affinity. Pharmacol Biochem Behav 37:371–373Google Scholar
  23. Sokoloff P, Giros B, Martres MP, Bouthenet ML, Schwartz JC (1990) Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 347:146–151Google Scholar
  24. Spear LP, Kirstein CL, Bell J, Yoottanasumpun V, Greenbaum R, O'Shea J, Hoffmann H, Spear NE (1989a) Effects of prenatal cocaine exposure on behavior during the early postnatal period. Neurotoxicol Teratol 11:57–63Google Scholar
  25. Spear LP, Kirstein CL, Frambes NA (1989b) Cocaine effects on the developing central nervous system: behavioral, psychopharmacological and neurochemical studies. Ann NY Acad Sci 562:290–307Google Scholar
  26. Spear LP, Kirstein CL, Frambes NA, Moody CA (1990) Neurobehavioral teratogenicity of gestational cocaine exposure. NIDA Res Monogr 95:232–238Google Scholar
  27. Starr BS, Starr MS (1986) Differential effects of dopamine D1 and D2 agonists and antagonists on velocity of movement, rearing and grooming in the mouse. Neuropharmacology 25:455–463Google Scholar
  28. Staton DM, Solomon P (1984) Microinjections ofd-amphetamine into the nucleus accumbens and caudate-putamen differentially affect stereotypy and locomotion in the rat. Phsyiol Psychol 12:159–162Google Scholar
  29. White FJ, Bednarz LM, Wachtel SR, Hjorth S, Brooderson RJ (1988) Is stimulation of both D1 and D2 receptors necessary for the expression of dopamine-mediated behaviors? Pharmacol Biochem Behav 30:189–193Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • C. A. Moody
    • 1
  • N. A. Frambes
    • 1
  • L. P. Spear
    • 1
  1. 1.Department of Psychology and Center for Developmental PsychobiologySUNY-BinghamtonBinghamtonUSA

Personalised recommendations