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. 1989 Feb 7;160(3):377-84. doi: 10.1016/0014-2999(89)90093-9.

Abstract

A range of 3- and 6-substituted 1-phenyl-1H-3-benzazepine analogues of SK&F 38393 with D-1 agonist activity were compared for their behavioural effects in the intact adult rat and for their relative affinities for D-1 and D-2 dopamine receptors in vitro. All compounds showed selective affinity for D-1 receptors and induced prominent grooming behaviour, but those with the lower D-1:D-2 selectivity ratios also induced additional episodes of non-stereotyped sniffing, locomotion and rearing. No vacuous chewing was noted. There were marked differences in in vivo potency, extending over a 100-fold range. These responses to the most potent agonist, SK&F 77434 (3N-allyl-SK&F 38393) were reduced enantioselectively by the D-1 antagonist R-SK&F 83566. They were also reduced enantioselectively by the D-2 antagonist R-piquindone, but this pretreatment additionally released a marked vacuous chewing response to SK&F 77434. Prominent grooming may be a characteristic behavioural response to a range of D-1 agonists. It is suggested that there may be at least two forms of functional interaction between D-1 and D-2 systems, manifested concurrently in distinct elements of behaviour: one co-operative, as in the regulation of grooming, and with correlates in the regulation of pallidal neural activity; the other oppositional, as in the regulation of vacuous chewing, and with correlates in the regulation of striatal adenylate cyclase activity.

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
  • Benzazepines / pharmacology
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Dopamine Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Grooming / drug effects*
  • Isoquinolines / pharmacology
  • Male
  • Radioligand Assay
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects*
  • Spiperone / metabolism
  • Stereotyped Behavior / drug effects*

Substances

  • Benzazepines
  • Dopamine Agents
  • Isoquinolines
  • Receptors, Dopamine
  • Spiperone
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Ro 22-1319