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Comparison of the D1-dopamine agonists SKF-38393 and A-68930 in neonatal 6-hydroxydopamine-lesioned rats: behavioral effects and induction of c-fos-like immunoreactivity.

Abstract
Administration of the selective D1-dopamine receptor agonist 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (SKF-38393) to neonatal 6-hydroxydopamine-lesioned rats results in profound behavioral manifestations and induction of striatal c-fos-like immunoreactivity. The full D1-dopamine agonist I,[R,S]1-aminomethyl-3,4-dihydro-5,6-dihydroxy-3-phenyl-1H-2-benzopyran hydrochloride (A-68930), like SKF-38393, produced a dose-dependent, D1-selective increase in locomotor activity and striatal c-fos-like immunoreactivity. These responses were antagonized by a D1-dopamine antagonist, but not by a D2-dopamine antagonist. A-68930 produced locomotor activation at a lower dose than SKF-38393, but no dose of A-68930 was able to produce the magnitude of locomotor activation seen with SKF-38393. Both A-68930 and SKF-38393 induced similar stereotyped behaviors and possessed similar propensities to induce self-injurious behavior in neonatally lesioned rats; however, A-68930 was significantly more potent than SKF-38393 in inducing these behaviors. When either SKF-38393 or A-68930 were administered repeatedly at 2-week intervals, behavioral sensitization (priming) occurred. However, unlike SKF-38393, a high dose of A-68930 produced seizure activity and markedly desensitized D1-dopamine receptor activation for up to 3 days after administration. These results with A-68930 provide additional evidence that the specific behavioral and biochemical responses observed in neonatally lesioned rats after SKF-38393 administration are due to actions on D1-dopamine receptors, and indicate that A-68930 provides a new tool for investigating D1-dopamine receptor function.
AuthorsK B Johnson, H E Criswell, K F Jensen, P E Simson, R A Mueller, G R Breese
JournalThe Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 262 Issue 2 Pg. 855-65 (Aug 1992) ISSN: 0022-3565 [Print] United States
PMID1354257 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Benzazepines
  • Chromans
  • Dopamine Agents
  • Proto-Oncogene Proteins c-fos
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Oxidopamine
  • A 68930
Topics
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (pharmacology)
  • Animals
  • Animals, Newborn
  • Behavior, Animal (drug effects)
  • Benzazepines (pharmacology)
  • Brain Chemistry (drug effects)
  • Chromans (pharmacology)
  • Dopamine Agents (pharmacology)
  • Dose-Response Relationship, Drug
  • Female
  • Motor Activity (drug effects)
  • Oxidopamine (toxicity)
  • Proto-Oncogene Proteins c-fos (analysis, immunology)
  • Rats
  • Receptors, Dopamine (drug effects, physiology)
  • Receptors, Dopamine D1
  • Stereotyped Behavior (drug effects)

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