The effects of dopamine D3 agonists and antagonists in a nonhuman primate model of tardive dyskinesia
| Autor: | Linda Peacock, Peter Malik, Maibritt B. Andersen |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
Agonist Dyskinesia Drug-Induced medicine.medical_specialty Indoles medicine.drug_class Agonist-antagonist Clinical Biochemistry Toxicology Tardive dyskinesia Biochemistry Dopamine agonist Behavioral Neuroscience Pramipexole Dopamine receptor D3 Tetrahydroisoquinolines Dopamine receptor D2 Internal medicine Nitriles medicine Animals Cebus Benzothiazoles Biological Psychiatry Pharmacology Receptors Dopamine D2 business.industry Receptors Dopamine D1 Receptors Dopamine D3 Benzazepines medicine.disease Dopamine D2 Receptor Antagonists Thiazoles Endocrinology Dyskinesia Dopamine Agonists Dopamine Antagonists Female medicine.symptom business medicine.drug |
| Zdroj: | Pharmacology Biochemistry and Behavior. 78:805-810 |
| ISSN: | 0091-3057 |
| DOI: | 10.1016/j.pbb.2004.05.019 |
| Popis: | Tardive dyskinesia (TD), a serious complication of antipsychotic dopamine (DA) antagonist treatment, has been hypothesised to develop due to a dominant DA D1 relative to DA D2 receptor function. Recent genetic and pharmacological studies implicate the DA D3 receptor in TD. The present study examined the role of the DA D3 receptor in relation to the DA D1/D2 imbalance hypothesis of TD in nonhuman primates. Eight Cebus monkeys displaying mild to severe TD due to previous chronic exposure to DA D2 antagonists were acutely injected with SKF 81297 (DA D1 agonist) 0.3 and 0.6 mg/kg, pramipexole (DA D3>D2 agonist) 0.025–0.1 mg/kg, CIS-8-OH-PBZI (DA D3 agonist) 5–10 mg/kg and SB-27701-A (DA D3 antagonist) 1–5 mg/kg and rated for oral dyskinesia. SKF 81297, 0.3 and 0.6 mg/kg, exacerbated TD. Pramipexole and CIS-8-OH-PBZI reduced SKF 81297-induced TD, while SB-27701-A had no effect. When administered alone, SB-27701-A increased TD relative to placebo, while pramipexole and CIS-8-OH-PBZI had no significant effect. Pramipexole did, however, ameliorate TD in those monkeys with severe TD. These results point towards a role of the DA D3 receptor in TD, but indicate that the DA D2 receptor may also play an essential role. |
| Databáze: | OpenAIRE |
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