| Abstract | Previous studies have demonstrated that both direct- and indirect-acting dopamine (DA) receptor agonists excite type II neurons in the anterior caudate (CN) by stimulation of DA receptors belonging to the D2 receptor subfamily (D2, D3, D4 receptor subtypes). In the present study, pramipexole, a D3-preferring DA agonist effective in treating Parkinson's disease, excited type II anterior CN neurons. As with other direct-acting agonists, excitation of the CN neurons occurred only at doses above those that silenced DA neurons in the substantia nigra pars compacta (SNPC). Although more potent than pramipexole in inhibiting SNPC cells, PNU-91356A, a D2-preferring agonist, did not excite type II CN cells. The D3-preferring antagonist (+)-AJ76 was weaker than haloperidol, a D2-preferring antagonist, in reversing the effects of amphetamine on firing rates in dopaminergic neurons in both the SNPC and the CN. However, in relationship to its potency in the SNPC, (+)-AJ76 was more potent than haloperidol in the CN. PNU-101387, a selective D4 antagonist, did not alter amphetamine-induced stimulation of type II CN neurons. We conclude that DA agonists may excite type II anterior CN neurons via D3 receptor activation. The stimulation of these neurons may contribute to the anti-parkinsonian effects of pramipexole. |
| Authors | M F Piercey, D K Hyslop, W E Hoffmann
(Affiliation: CNS Research, Pharmacia and Upjohn, Inc., Kalamazoo, MI 49001, USA.)
|
| Journal | Brain research
(Brain Res)
Vol. 762
Issue 1-2
Pg. 19-28
(Jul 11 1997)
ISSN: 0006-8993 NETHERLANDS |
| PMID | 9262154
(Publication Type: Journal Article)
|
| Chemical References |
- Aminoquinolines
- Benzothiazoles
- Dopamine Agonists
- Dopamine Antagonists
- Drd3 protein, rat
- Imidazoles
- Receptors, Dopamine D2
- Receptors, Dopamine D3
- Receptors, Serotonin
- Receptors, Serotonin, 5-HT1
- Serotonin Agonists
- Tetrahydronaphthalenes
- Thiazoles
- pramipexol
- 5-propylamino-5,6-dihydro-4H-imidazo(4,5,1-ij)quinolin-2(1H)-one
- Haloperidol
- 8-Hydroxy-2-(di-n-propylamino)tetralin
- 5-methoxy-1-methyl-2-(n-propylamino)tetralin
- Quinpirole
|
| Topics |
- 8-Hydroxy-2-(di-n-propylamino)tetralin
(pharmacology)
- Aminoquinolines
(pharmacology)
- Animals
- Benzothiazoles
- Caudate Nucleus
(chemistry, cytology)
- Dopamine Agonists
(pharmacology)
- Dopamine Antagonists
(pharmacology)
- Dose-Response Relationship, Drug
- Electrophysiology
- Haloperidol
(pharmacology)
- Imidazoles
(pharmacology)
- Neurons
(chemistry, drug effects, physiology)
- Quinpirole
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Receptors, Dopamine D2
(agonists, antagonists & inhibitors, physiology)
- Receptors, Dopamine D3
- Receptors, Serotonin
(drug effects)
- Receptors, Serotonin, 5-HT1
- Serotonin Agonists
(pharmacology)
- Tetrahydronaphthalenes
(pharmacology)
- Thiazoles
(pharmacology)
|
