Conservation of behavioural topography to dopamine D1-like receptor agonists in mutant mice lacking the D1A receptor implicates a D1-like receptor not coupled to adenylyl cyclase

Neuroscience. 1999;93(4):1483-9. doi: 10.1016/s0306-4522(99)00297-3.


Though D1-like dopamine receptors [D1A/B] are defined in terms of linkage to the stimulation of adenylyl cyclase, with D1A assumed to be the functionally prepotent subtype, evidence suggests the existence of another, novel D1-like receptor without such coupling. To investigate these issues we challenged mutant mice having targeted gene deletion of the D1A receptor with selective agonists and used an ethologically-based assessment technique to resolve resultant behavioural topography. D1-like-dependent behaviour was substantially conserved in D1A-null mice relative to wild-types following challenge with each of two selective D1-like agents: A 68930 (0.068-2.0 mg/kg s.c.) which exhibits full efficacy to stimulate adenylyl cyclase, and SKF 83959 (0.016-2.0 mg/kg s.c.) which fails to stimulate adenylyl cyclase, and indeed inhibits the stimulation of adenylyl cyclase induced by dopamine. Furthermore, responsivity to the selective D2-like agonist RU 24213 (0.1-12.5 mg/kg s.c.) was conserved in D1A-null mice, indicating the integrity of D1-like:D2-like interactions at the level of behaviour. These data are consistent with behavioural primacy of a D1-like receptor other than D1A [or D1B] that is coupled to a transduction system other than/additional to adenylyl cyclase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / analogs & derivatives
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • Adenylyl Cyclases / metabolism*
  • Animals
  • Behavior, Animal / drug effects*
  • Brain / enzymology
  • Brain Chemistry*
  • Chromans / pharmacology
  • Dopamine Agonists / pharmacology
  • Female
  • Grooming / drug effects
  • Locomotion / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenethylamines / pharmacology
  • Receptors, Dopamine D1 / agonists*
  • Receptors, Dopamine D1 / genetics*
  • Receptors, Dopamine D2 / agonists
  • Receptors, Dopamine D2 / physiology


  • Chromans
  • Dopamine Agonists
  • Phenethylamines
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride
  • SK&F 83959
  • A 68930
  • Adenylyl Cyclases