Responses to selective D-1 and D-2 agonists after repeated treatment with selective D-1 and D-2 antagonists

Pharmacol Biochem Behav. 1988 Jun;30(2):463-9. doi: 10.1016/0091-3057(88)90481-9.

Abstract

This study was aimed at achieving a better understanding of the functional role of D-1 and D-2 receptors in some dopamine-mediated behaviors. Hypermotility, grooming behavior and stereotyped behavior were induced, respectively, by LY 171555 (D-2 agonist), SKF 38393 (D-1 agonist) and apomorphine (mixed agonist). Acute pretreatment either with the D-1 selective antagonist SCH 23390 (0.02 mg/kg) or with the D-2 receptor blocker YM 09151-2 (0.02 mg/kg, IP) blocked all these behaviors, suggesting the existence of functional interactions between D-1 and D-2 receptors. Striatal membranes prepared from rats receiving repeated administrations with SCH 23390 (0.05 mg/kg, twice daily for 21 days) showed an increase in the number of D-1 but not of D-2 receptors. On the contrary the repeated treatments with YM 09151-2 increased only the Bmax values of D-2 receptors. While the D-1 supersensitive rats showed only enhancement of apomorphine-induced stereotyped behavior, the D-2 supersensitive rats exhibited an increase of both apomorphine-elicited stereotypy and LY 171555-elicited hypermotility. SKF 38393-induced grooming was unaffected by any pretreatments. Moreover when D-2 supersensitive rats were acutely pretreated with SCH 23390, the enhancement of apomorphine-induced stereotyped behavior was abolished. It is concluded that the behavioral expression of D-1 receptor supersensitivity requires the simultaneous activation of D-1 and D-2 receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Animals
  • Apomorphine / pharmacology*
  • Benzazepines / pharmacology*
  • Ergolines / pharmacology*
  • Grooming / drug effects
  • Locomotion / drug effects
  • Male
  • Quinpirole
  • Radioligand Assay
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects*
  • Stereotyped Behavior / drug effects

Substances

  • Benzazepines
  • Ergolines
  • Receptors, Dopamine
  • Quinpirole
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Apomorphine