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.
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Authors | K B Johnson, H E Criswell, K F Jensen, P E Simson, R A Mueller, G R Breese |
Journal | The 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 |
PMID | 1354257
(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.)
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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
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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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