Advertisement

Psychopharmacology

, Volume 109, Issue 1–2, pp 41–48 | Cite as

Parametric and pharmacological analyses of the enhanced grooming response elicited by the D1 dopamine receptor agonist SKF 38393 in the rat

  • Stephen R. Wachtel
  • Richard J. Brooderson
  • Francis J. White
Original Investigations

Abstract

The present report investigated several parametric and pharmacological aspects of the enhanced self-grooming behavior of rats following systemic administration of the selective D1 dopamine (DA) receptor agonist SKF 38393. The amount of time that rats spent grooming themselves was measured continuously for 30 min following drug administration to provide a quantitative measure of the drug-induced behavior. SKF 38393 increased the amount of grooming in a dose-dependent manner (0.5–16 mg/kg, SC). The onset of this effect required at least 5 min and it persisted for at least 60 min. The ability of SKF 38393 to enhance grooming was shared by R-SKF 38393, but not S-SKF 38393, consistent with the affinities of these enantiomers for the D1 DA receptor. Unlike SKF 38393, the peripheral D1 agonist fenoldopam (SKF 82526) failed to cause an increased grooming response, suggesting a central site of action for elicitation of this behavior. The SKF 38393-induced increase in grooming was competitively antagonized by the D1 selective antagonist SCH 23390 (0.5 mg/kg, SC). Although the D2 DA receptor-selective antagonist eticlopride reduced SKF 38393-elicited grooming, this antagonism appeared to be of a physiological rather than pharmacological nature. When eticlopride was coadministered with the non-selective (mixed) D1/D2 agonist apomorphine, an increase in grooming behavior similar to that produced by SKF 38393 was observed. Inactivation of D1 and D2 DA receptors produced by pretreatment with the irreversible antagonistN-ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline (EEDQ), at a dose which reduces D1 and D2 receptor density by ≥50% (8.0 mg/kg, IP), reduced SKF 38393-induced grooming by approximately 50%. Prior protection of D1 receptors by SCH 23390 completely prevented the effect of EEDQ whereas prior protection of D2 receptors by eticlopride did not. These results demonstrate that enhanced grooming behavior elicited by dopamine agonists in rats, when measured as the amount of time spent grooming, provides a reliable, quantifiable index of selective D1 DA receptor activation in the CNS. In addition, this behavior does not appear to require concurrent stimulation of D2 DA receptors by endogenous DA.

Key words

D1 receptors D2 receptors Grooming SKF 38393 Fenoldopam SCH 23390 Synergism 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ajima A, Yamaguchi T, Kato T (1990) Modulation of acetylcholine release by D1, D2 dopamine receptors in rat striatum under freely moving conditions. Brain Res 518:193–198CrossRefPubMedGoogle Scholar
  2. Andersen PH (1988) Differential effects of EEDQ on the dopamine D-1 receptor in vivo and in vitro. Eur J Pharmacol 152:153–156CrossRefPubMedGoogle Scholar
  3. Arnt J, Hyttel J, Meier E (1988) Inactivation of dopamine D-1 or D-2 receptors differentially inhibits stereotypies induced by dopamine agonists in rats. Eur J Pharmacol 155:37–47CrossRefPubMedGoogle Scholar
  4. Asin KE, Bednarz LM (1990) Behavioral interactions between muscimol and compounds selective for the D1 and D2 dopamine receptor subtypes. Neurosci Lett 113:286–291CrossRefPubMedGoogle Scholar
  5. Berridge KC (1990) Comparative fine structure of action: rules of form and sequence in the grooming patterns of six rodent species. Behavior 113:21–56Google Scholar
  6. Braun AR, Chase TN (1986) Obligatory D1–D2 receptor coactivation and the generation of dopamine agonist related behaviors. Eur J Pharmacol 131:301–306CrossRefPubMedGoogle Scholar
  7. Carlson JH, Bergstrom DA, Demo SD, Walters JR (1988) Acute reduction of dopamine levels alters responses of basal ganglia neurons to selective D-1 and D-2 dopamine receptor stimulation. Eur J Pharmacol 152:289–300CrossRefPubMedGoogle Scholar
  8. Chandler CJ, Wohab W, Starr BS, Starr MS (1990) Motor depression: a new role for D1 receptors? Neuroscience 38:437–445CrossRefPubMedGoogle Scholar
  9. 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
  10. Flaim KE, Gessner GW, Crooke ST, Sarau HM, Weinstock J (1985) Binding of a novel dopaminergic agonist radioligand [3H]-fenoldopam (SKF 82526) to D-1 receptors in rat striatum. Life Sci 36:1427–1436CrossRefPubMedGoogle Scholar
  11. Fuxe K, Meller E, Goldstein M, Benfenati F, Agnati LF (1986) Analysis of [3H]spiperone binding sites in the rat striatum and frontoparietal cortex by means of quantitative receptor autoradiography after inactivation of dopamine receptors by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in vivo: selective protection by sulpiride in the striatum. Neurosci Lett 64:163–168CrossRefPubMedGoogle Scholar
  12. Gandolfi O, Dall'Olio R, Vaccheri A, Roncada P, Montanaro N (1988) Responses to selective D-1 and D-2 agonists after repeated treatment with selective D-1 and D-2 antagonists. Pharmacol Biochem Behav 30:463–469CrossRefPubMedGoogle Scholar
  13. Giorgio O, De Montis G, Porceddu ML, Mele S, Calderini G, Toffano G, Biggio G (1987) Developmental and age-related changes in D1-dopamine receptors and dopamine content in the rat striatum. Devel Brain Res 35:283–290CrossRefGoogle Scholar
  14. Hamblin MW, Creese I (1983) Behavioral and radioligand binding evidence for irreversible dopamine receptor blockade by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline. Life Sci 32:2247–2255CrossRefPubMedGoogle Scholar
  15. Hu X-T, Wachtel SR, Galloway MP, White FJ (1990) Lesions of the nigrostriatal dopamine projection increase the inhibitory effects of D1 and D2 dopamine agonists on caudate-putamen neurons and relieve D2 receptors from the necessity of D1 receptor stimulation. J Neurosci 10:2318–2329PubMedGoogle Scholar
  16. Hyttel J (1987) Age related decrease in the density of dopamine D1 and D2 receptors in corpus striatum of rats. Pharmacol Toxicol 61:126–129PubMedGoogle Scholar
  17. Johansen PA, Hu X-T, White FJ (1991) Relationship between D1 dopamine receptors, adenylate cyclase and the electrophysiological responses of rat nucleus accumbens neurons. J Neural Transm 86:97–113CrossRefGoogle Scholar
  18. Lategan AJ, Mavridis M, Marien M, Colpaert FC (1989) The effects of locus coeruleus lesions on behaviours induced by putative D1 and D2 receptor agonists. Neurosci Res Commun 5:63–72Google Scholar
  19. Meller E, Bohmaker K, Goldstein M, Friedhoff AJ (1985) Inactivation of D1 and D2 dopamine receptors by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in vivo: selective protection by neuroleptics. J Pharmacol Exp Ther 233:656–662PubMedGoogle Scholar
  20. Molloy AG, Waddington JL (1984) Dopaminergic behaviour stereospecifically promoted by the D1 agonist R-SK&F 38393 and selectively blocked by the D1 antagonist SCH 23390. Psychopharmacology 82:409–410CrossRefPubMedGoogle Scholar
  21. Molloy AG, Waddington JL (1985) Sniffing, rearing and locomotor responses to the D-1 dopamine agonist R-SK&F 38393 and to apomorphine: differential interactions with the selective D-1 and D-2 antagonists SCH 23390 and metoclopramide. Eur J Pharmacol 108:305–308CrossRefPubMedGoogle Scholar
  22. Molloy AG, Waddington JL (1987a) Assessment of grooming and other behavioural responses to the D-1 dopamine receptor agonist SK & F 38393 and its R- and S-enantiomers in the intact adult rat. Psychopharmacology 92:164–168Google Scholar
  23. Molloy AG, Waddington JL (1987b) Pharmacological characterization in the rat of grooming and other behavioral responses to the D1 dopamine receptor agonist R-SK&F 38393. J Psychopharmacol 1:177–183Google Scholar
  24. Molloy AG, Waddington JL (1988) Behavioral responses to the selective D1-dopamine receptor agonist R-SK&F 38393 and the selective D2-agonist RU 24213 in young compared with aged rats. Br J Pharmacol 95:335–342PubMedGoogle Scholar
  25. Morelli M, Mennini T, Cagnotto A, Toffano G, Di Chiara G (1990) Quantitative autoradiological analysis of the age-related modulation of central dopamine D1 and D2 receptors. Neuroscience 36:403–410CrossRefPubMedGoogle Scholar
  26. Murray AM, Waddington JL (1989) The induction of grooming and vacuous chewing by a series of selective D-1 dopamine receptor agonists: two directions of D-1: D-2 interaction. Eur J Pharmacol 160:377–384CrossRefPubMedGoogle Scholar
  27. Neisewander JL, Lucki I, McGonigle P (1991a) Behavioral and neurochemical effects of chronic administration of reserpine and SKF-38393 in rats. J Pharmacol Exp Ther 257:850–860PubMedGoogle Scholar
  28. Neisewander JL, Ong A, McGonigle P (1991b) Anatomical localization of dopamine D1 receptor-mediated behaviors in rats using the irreversible antagonist EEDQ. Soc Neurosci Abst 17:677Google Scholar
  29. Norman AB, Wachendorf TJ, Sanberg PR (1989) Differential effect of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on [3H]SCH 23390 and [3H]forskol in binding in rat striatum. Life Sci 44:831–836CrossRefPubMedGoogle Scholar
  30. Nowak G, Arnt J, Hyttel J (1988) EEDQ, a tool for ex vivo measurement of occupancy of D-1 and D-2 dopamine receptors. Eur J Pharmacol 153:309–311CrossRefPubMedGoogle Scholar
  31. O'Boyle KM, Waddington JL (1984a) Loss of rat striatal dopamine receptors with ageing is selective for D-2 but not D-1 sites: association with increased non-specific binding of the D-1 ligand [3H]piflutixol. Eur J Pharmacol 105:171–174CrossRefPubMedGoogle Scholar
  32. O'Boyle KM, Waddington JL (1984b) Selective and stereospecific interactions of R-SK&F 38393 with [3H]piflutixol but not [3H]spiperone binding to striatal D1 and D2 dopamine receptors: comparisons with SCH 23390. Eur J Pharmacol 98:433–436CrossRefPubMedGoogle Scholar
  33. Ross SB, Jackson DM, Wallis EM, Edwards SR (1988) Enhancement by a single dose of reserpine (plus alpha methyl-p-tyrosine) of the central stimulatory effects evoked by dopamine D-1 and D-2 agonists in the mouse. Naunyn-Schmiedeberg's Arch Pharmacol 337:512–518CrossRefGoogle Scholar
  34. Sachs BD (1988) The development of grooming and its expression in adult animals. In: Colbern DL, Gispen WH (eds) Neural Mechanisms and biological significance of grooming behavior. Ann NY Acad Sci 525:1–17Google Scholar
  35. Saller CF, Kreamer LD, Adamovage LA, Salama AI (1989) Dopamine receptor occupancy in vivo: measurement using N-ethoxycarbonyl-2-ethoxy-1,2-dihydriquinoline (EEDQ). Life Sci 45:917–929CrossRefPubMedGoogle Scholar
  36. Setler PE, Sarau JM, Zirkle CL, Saunders JL (1978) The central effects of a novel dopamine agonist. Eur J Pharmacol 50:419–430CrossRefPubMedGoogle Scholar
  37. Sidhu A, Kebabian JW (1985) An iodinated ligand identifying the D-1 dopamine receptor. Eur J Pharmacol 113:437–440CrossRefPubMedGoogle Scholar
  38. Sokoloff P, Giros B, Martres M-P, Bouthenet M-L, Schwartz J-C (1990) Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 347:146–151CrossRefPubMedGoogle Scholar
  39. Starr BS, Starr MS (1986a) Differential effects of dopamine D1 and D2 agonist and antagonists on velocity of movement, rearing and grooming in the mouse. Neuropharmacology 25:455–463CrossRefPubMedGoogle Scholar
  40. Starr BS, Starr MS (1986b) Grooming in the mouse is stimulated by the dopamine D1 agonist SKF 38393 and by low doses of the D1 antagonist SCH 23390, but is inhibited by dopamine D2 agonists, D2 antagonists and high doses of SCH 23390. Pharmacol Biochem Behav 24:837–839CrossRefPubMedGoogle Scholar
  41. Starr BS, Starr MS, Kilpatrick IC (1987) Behavioral role of dopamine D1 receptors in the reserpine-treated mouse. Neuroscience 22:179–188CrossRefPubMedGoogle Scholar
  42. Sunahara RK, Guan H-C, O'Dowd BF, Seeman P, Laurier LG, Ng G, George SR, Torchia J, Van Tol HHM, Niznik HB (1991) Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature 350:614–619CrossRefPubMedGoogle Scholar
  43. Tallarida RJ, Jacob LS (1979) The dose-response relation in pharmacology. Springer, Berlin Heidelberg New YorkGoogle Scholar
  44. Van Tol HHM, Bunzow JR, Guan H-C, Sunahara RK, Seeman P, Niznik HB, Civelli O (1991) Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature 350:610–614CrossRefPubMedGoogle Scholar
  45. Vasse M, Protais P (1988) Increased grooming is induced by apomorphine in mice treated with discriminant benzamide derivatives. Eur J Pharmacol 156:1–11CrossRefPubMedGoogle Scholar
  46. Wachtel SR, White FJ (1991) The D1 dopamine receptor antagonist SCH 23390 exerts agonist-like effects on rat nucleus accumbens neurons. Soc Neurosci Abstr 17:1353Google Scholar
  47. Wachtel SR, Hu X-T, Galloway MP, White FJ (1989) D1 dopamine receptor stimulation enables the postsynaptic, but not autoreceptor, effects of D2 dopamine agonists in nigrostriatal and mesoaccumbens dopamine systems. Synapse 4:327–346CrossRefPubMedGoogle Scholar
  48. Waddington JL (1989) Functional interactions between D-1 and D-2 dopamine receptor systems: their role in the regulation of psychomotor behaviour, putative mechanisms, and clinical relevance. J Psychopharmacol 3:54–63Google Scholar
  49. Waddington JL, O'Boyle KM (1987) The D-1 dopamine receptor and the search for its functional role: from neurochemistry to behaviour. Rev Neurosci 1:157–184Google Scholar
  50. Waddington JL, Molloy AG, O'Boyle KM, Pugh MT (1990) Aspects of stereotyped and non-stereotyped behaviour in relation to dopamine receptor subtypes. In: Cooper SJ, Dourish CT (eds) Neurobiology of stereotyped behaviour. Oxford University Press, Oxford, pp 64–90Google Scholar
  51. White FJ (1987) D-1 dopamine receptor stimulation “enables” the inhibitory effects of the D-2 agonist quinpirole on rat nucleus accumbens neurons. Eur J Pharmacol 135:101–105CrossRefPubMedGoogle Scholar
  52. White FJ, Wachtel SR, Johansen PA, Einhorn LE (1987) Electrophysiological studies in the rat mesoaccumbens dopamine system: focus on dopamine receptor subtypes, interactions and the effects of cocaine. In: Chiodo LA, Freeman AS (eds) Neurophysiology of dopaminergic systems: current status and future perspectives. Lakeshore Press, Detroit, pp 317–365Google Scholar
  53. 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 30:189–193CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Stephen R. Wachtel
    • 1
  • Richard J. Brooderson
    • 1
  • Francis J. White
    • 1
  1. 1.Departments of Psychiatry and PharmacologyWayne State University School of Medicine, Neuropsychopharmacology Laboratory, Lafayette ClinicDetroitUSA

Personalised recommendations