Psychopharmacology

, Volume 109, Issue 4, pp 403–409

Differential antagonism of the effects of dopamine D1-receptor agonists on feeding behavior in the rat

  • Philip Terry
  • Jonathan L. Katz
Original Investigations

Abstract

A series of experiments was conducted to examine the effects of dopamine D1 receptor agonists on food intake in rats. In the first experiment, the D1 agonist SKF 38393 (3.0–30.0 mg/kg) dose-dependently suppressed feeding during a 40 min food-access period, both in food-deprived rats and in non-deprived rats fed a highly palatable diet. Non-deprived rats were more sensitive to these effects of SKF 38393. Using the limited-access, food-deprivation procedure, a comparison was made between the anorectic effects of three D1 agonists with differing intrinsic efficacies and receptor selectivities. Rank order of potencies for reducing food intake was SKF 82958 > SKF 77434 > SKF 38393 (ED50 values: 0.7, 3.6 and 15.7 mg/kg, respectively). Dose-related, surmountable antagonism by the D1 antagonist SCH 23390 (0.01 and 0.03 mg/kg) was only obtained with SKF 82958 (0.1–10.0 mg/kg). In contrast to the other compounds, the effects of SKF 38393 were not appreciably altered by the D1 antagonist. The effects of SKF 82958 were also antagonized by the D2 receptor antagonist spiperone (0.05 and 0.1 mg/kg), although not in a dose-dependent manner. The present results support a role for D1 receptors in central feeding mechanisms. They also suggest that the effects of SKF 38393 on feeding may not be mediated exclusively by the D1 receptor and, further, that SKF 38393 may not serve well in behavioral studies as a prototypical D1 agonist. The results also demonstrate the need for comparisons among several compounds in studies of D1 mediated behavioral effects.

Key words

Dopamine D1 D2 SKF 38393 SKF 77434 SKF 82958 SCH 23390 Spiperone Feeding Behavior Rat 

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References

  1. Andersen PH, Jansen JA (1990) Dopamine receptor agonists: selectivity and D1 receptor efficacy. Eur J Pharmacol 188:335–347Google Scholar
  2. Andersen PH, Nielsen EB, Scheel-Kruger J, Jansen JA, Hohlweg R (1987) Thienopyridine derivatives identified as the first selective, full efficacy dopamine D1 receptor agonists. Eur J Pharmacol 137:291–292Google Scholar
  3. Andersen PH, Gingrich JA, Bates MD, Dearry A, Falardeau P, Senogles SE, Caron MG (1990) Dopamine receptor subtypes: beyond the D1/D2 classification. TINS 11:231–236Google Scholar
  4. Arnt J, Hyttel J (1988) Behavioral differentiation between effects elicited at dopamine D-1 and D-2 receptors in rats with normosensitive DA receptors. Pharmacopsychiatry 21:24–27Google Scholar
  5. Arnt J, Bogeso KP, Hyttel J, Meier E (1988a) Relative dopamine D1 and D2 receptor affinity and efficacy determine whether dopamine agonists induce hyperactivity or oral stereotypy in rats. Pharmacol Toxicol 62:121–130Google Scholar
  6. Arnt J, Hyttel J, Meier E (1989b) Inactivation of D-1 or D-2 receptors differentially inhibits stereotypies induced by dopamine agonists in rats. Eur J Pharmacol 155:37–47Google Scholar
  7. Barone P, Davis TA, Braun A, Chase TN (1986) Dopaminergic mechanisms and motor function: characterization of D1 and D2 dopamine receptor interactions. Eur J Pharmacol 123:109–114Google Scholar
  8. Barzaghi R, Groppetti A, Mantegazza P, Muller EE (1973) Reduction of food intake by apomorphine: a pimozide-sensitive effect. J Pharm Pharmacol 25:909–911Google Scholar
  9. Braun AR, Chase TN (1986) Obligatory D1/D2 receptor interactions in the generation of dopamine agonist related behaviors. Eur J Pharmacol 131:301–306Google Scholar
  10. Brent PJ (1991) Behavioural effects of selective dopamine D1 and D2 agonists and antagonists in guinea pigs. Psychopharmacology 104:201–207Google Scholar
  11. Clarke 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 1:347–388Google Scholar
  12. Clifton PG, Rusk IN, Cooper SJ (1991) Effects of dopamine D1 and dopamine D2 antagonists on the free feeding and drinking patterns of rats. Behav Neurosci 105:272–281Google Scholar
  13. Cooper SJ, Francis J, Rusk IN (1990) The anorectic effect of SK&F 38393, a selective dopamine D1 receptor agonist: a microstructural analysis of feeding and related behavior. Psychopharmacology 100:182–187Google Scholar
  14. Finney DJ (1964) Statistical methods in biological assay, 2nd edn. Hafner, New YorkGoogle Scholar
  15. Gilbert DB, Cooper SJ (1985) Analysis of dopamine D1 and D2 receptor involvement ind- andl-amphetamine-induced anorexia in rats. Brain Res Bull 15:385–389Google Scholar
  16. Horita A, Carino MA (1991) D1 agonist, SKF 38393, but not a D2 agonist, produces a cholinergically-mediated analeptic effect in rabbits. Pharmacol Biochem Behav 39:449–452Google Scholar
  17. Hyttel J (1983) SCH 23390: the first selective dopamine D1 antagonist. Eur J Pharmacol 91:153–154Google Scholar
  18. Iorio LC, Barnet A, Leitz FH, Houser VP, Korduba CA (1983) SCH 23390, a potential benzazepine antipsychotic with unique interactions on dopaminergic systems. J Pharmacol Exp Ther 226:462–468Google Scholar
  19. Johannson P, Levin E, Gunne L, Ellison G (1987) Opposite effects of a D1 and D2 agonist on oral movements in rats. Eur J Pharmacol 134:82–88Google Scholar
  20. Kamien JB, Goldberg LI, Woolverton WL (1987) Discriminative stimulus properties of D1 and D2 dopamine agonists in rats. J Pharmacol Exp Ther 242:804–811Google Scholar
  21. Kebabian JW, Calne DB (1979) Multiple receptors for dopamine. Nature 277:93–96Google Scholar
  22. Ladurelle N, Duterte-Boucher D, Costentin J (1991) Stimulation of D1 and D2 dopamine receptors produces additive anorectic effects. Fundam Clin Pharmacol 5:481–490Google Scholar
  23. Leibowitz SF (1975) Amphetamine: possible site and mode of action for producing anorexia in the rat. Brain Res 84:160–167Google Scholar
  24. Mailman RB, Schulz DW, Kilts CD, Lewis MH, Rollema H, Wyrick S (1986) The multiplicity of the D1 dopamine receptor. In: Breese GR, Creese I (eds) Neurobiology of central D1 receptors. Plenum Press, New York, pp 53–72Google Scholar
  25. Martin-Iverson MT, Dourish CT (1988) Role of dopamine D1 and D2 receptor subtypes in mediating dopamine agonist effects on food consumption in rats. Psychopharmacology 96:370–374Google Scholar
  26. Meller E, Kuga S, Friedhoff A, Goldstein M (1985) Selective D2 dopamine receptor agonists prevent catalepsy induced by SCH 23390, a selective D1 antagonist. Life Sci 36:1857–1864Google Scholar
  27. Molloy AG, Waddington JL (1984) Dopaminergic behavior stereospecifically promoted by the D1 agonist R-SK&F 38393 and selectively blocked by the D1 antagonist SCH 23390. Psychopharmacology 82:409–410Google Scholar
  28. Molloy AG, Waddington JL (1985) Sniffing, rearing and locomotor responses to the D1 dopamine agonist R-SK&F 38393 and to apomorphine: differential interactions with the selective D1 and D2 antagonists SCH 23390 and metoclopramide. Eur J Pharmacol 108:305–308Google Scholar
  29. Molloy AG, Waddington JL (1987) Assessment of grooming and other behavioural responses to the D1 receptor agonist SK&F 38393 and its R- and S-enantiomers in intact adult rats. Psychopharmacology 92:164–168Google Scholar
  30. Molloy AG, O'Boyle KM, Pugh MT, Waddington JL (1986) Locomotor behaviors in response to new selective D1 and D2 dopamine receptor agonists, and the influence of selective antagonists. Pharmacol Biochem Behav 25:249–253Google Scholar
  31. Morelli M, DiChiara G (1985) Catalepsy induced by SCH 23390 in rats. Eur J Pharmacol 117:179–185Google Scholar
  32. Murray AM, Waddington JL (1989) The induction of grooming and vacuous chewing by a series of selective D1 dopamine receptor agonists: two directions of D1:D2 interaction. Eur J Pharmacol 160:377–384Google Scholar
  33. Murray AM, Waddington JL (1990) New putative selective agonists at the dopamine D1 receptor: behavioural and neurochemical comparison of CY 208–243 with SK&F 101384 and SK&F 103243. Pharmacol Biochem Behav 35:105–110Google Scholar
  34. O'Boyle KM, Gaitanopoulos DE, Brenner M, Waddington JL (1989) Agonist and antagonist properties of benzazepine and thienopyridine derivatives at the D1 dopamine receptor. Neuropharmacology 28:401–405Google Scholar
  35. Pfeiffer FR, Wilson JW, Weinstock J, Kuo GY, Chambers PA, Holden KG, Hahn RA, Wardle JR, Tobia AJ, Setler PE, Sarau HM (1982) Dopaminergic activity of substituted 6-chloro-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines. J Med Chem 25:352–358Google Scholar
  36. Rapoza D, Woolverton WL (1991) Attenuation of the effects of cocaine on milk consumption in rats by dopamine antagonists. Pharmacol Biochem Behav 40:133–137Google Scholar
  37. Rosengarten H, Schweitzer JW, Friedhoff AJ (1983) Induction of oral dyskinesias in naive rats by D1 stimulation. Life Sci 33:2479–2482Google Scholar
  38. Rusk IN, Cooper SJ (1988) Profile of the selective dopamine D2 receptor agonist N-0437: its effects on palatability- and deprivation-induced feeding, and operant responding for food. Physiol Behav 44:545–553Google Scholar
  39. Rusk IN, Cooper SJ (1989a) The selective dopamine D1 agonist SK&F 38393: its effect on palatability- and deprivation-induced feeding, and operant responding for food. Pharmacol Biochem Behav 34:17–22Google Scholar
  40. Rusk IN, Cooper SJ (1989b) Microstructural analysis of the anorectic effect of N-0437, a highly selective dopamine D2 agonist. Brain Res 494:350–358Google Scholar
  41. Schneider LH, Gibbs J, Smith GP (1986) D-2 selective antagonists suppress sucrose sham feeding in the rat. Brain Res Bull 17:605–611Google Scholar
  42. Setler PE, Sarau HM, Zirckle CI, Saunders HJ (1978) The central effects of a novel dopamine agonist. Eur J Pharmacol 50:419–430Google Scholar
  43. Snedecor GW, Cochran WG (1967) Statistical methods, 6th edn. Iowa State University Press, Ames, IowaGoogle Scholar
  44. Starr BS, Starr MS (1986a) 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 24:837–839Google Scholar
  45. Starr BS, Starr MS (1986b) Differential effects of dopamine D1 agonists and antagonists on velocity of movement, rearing and grooming in the mouse. Neuropharmacology 25:455–463Google Scholar
  46. Stoof JC, Kebabian JW (1984) Two dopamine receptors: biochemistry, physiology and pharmacology. Life Sci 35:2281–2296Google Scholar
  47. 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 a higher affinity for dopamine than D1. Nature 350:614–619Google Scholar
  48. Treit D, Berridge KC (1990) A comparison of benzodiazepine, serotonin, and dopamine agents in the taste-reactivity paradigm. Pharmacol Biochem Behav 37:451–456Google Scholar
  49. Waddington JL, O'Boyle KM (1989) Drugs acting on brain dopamine receptors: a conceptual re-evaluation five years after the first selective D1 antagonist. Pharmacol Ther 43:1–52Google Scholar
  50. Waddington JL, Murray AM, Boyle KM (1988) New selective D1 and D2 receptor agonists as further probes for behavioral interactions between D1 and D2 systems. In: Beart P, Woodruff G, Jackson D (eds) Pharmacology and functional regulation of dopaminergic neurons. Macmillan, London, pp 117–123Google Scholar
  51. Weinstock J, Hieble JP, Wilson JW (1985) The chemistry and pharmacology of 3-benzazepine derivatives. Drugs Future 10:645–696Google Scholar
  52. Witkin JM, Schindler CW, Tella SR, Goldberg SR (1991) Interactions of haloperidol and SCH 23390 with cocaine and dopamine receptor subtype-selective agonists on schedule-controlled behavior of squirrel monkeys. Psychopharmacology 104:425–431Google Scholar
  53. Zarrindast MR, Owji AA, Hosseininia T (1991) Evaluation of dopamine receptor involvement in rat feeding behavior. Gen Pharmacol 22:1011–1016Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Philip Terry
    • 1
  • Jonathan L. Katz
    • 1
  1. 1.Psychobiology SectionNIDA Addiction Research CenterBaltimoreUSA

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