Differential regional and dose-related effects of asenapine on dopamine receptor subtypes
| Autor: | Erik H. F. Wong, Taylor Moran-Gates, Mohammed Shahid, Brian Henry, Frank I. Tarazi |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Caudate nucleus Hippocampus Dibenzocycloheptenes Heterocyclic Compounds 4 or More Rings Receptors Dopamine Rats Sprague-Dawley Internal medicine Basal ganglia Image Processing Computer-Assisted medicine Animals Asenapine Psychopharmacologic agent Receptor Brain Chemistry Cerebral Cortex Pharmacology Dose-Response Relationship Drug Receptors Dopamine D2 Chemistry Receptors Dopamine D1 Putamen Receptors Dopamine D4 Receptors Dopamine D3 Rats Neostriatum Endocrinology Dopamine receptor Autoradiography Antipsychotic Agents medicine.drug |
| Zdroj: | Psychopharmacology. 198:103-111 |
| ISSN: | 1432-2072 0033-3158 |
| Popis: | The novel psychopharmacologic agent, asenapine, has high affinity for a range of receptors including the dopaminergic receptors.We examined the long-term effects of multiple doses of asenapine on dopamine receptor subtypes: D(1)-like (D(1) and D(5)), D(2), D(3), and D(4).Rats were given asenapine 0.03, 0.1, or 0.3 mg/kg (subcutaneously, twice daily) or vehicle for 4 weeks. Receptor binding was determined by autoradiography from brain sections collected from the medial prefrontal cortex (mPFC), dorsolateral frontal cortex, caudate putamen (CPu), nucleus accumbens (NAc), and hippocampus (HIP).Four weeks of asenapine at 0.3 mg/kg significantly (P0.05) increased D(1)-like binding in the mPFC (by 26%), NAc (59%), and CPu (55%). Asenapine (0.1 and 0.3 mg/kg) also increased D(2) binding in mPFC (43% and 55%, respectively). All doses of asenapine dose-dependently increased D(2) binding in HIP (by 32%, 45%, and 63%, respectively). In contrast, only 0.3 mg/kg of asenapine significantly (P0.05) increased D(2) binding in the NAc (32%) and CPu (41%). Repeated treatment with 0.1 and 0.3 mg/kg of asenapine increased D(4) binding in the NAc (36% and 71%), CPu (27% and 70%), and HIP (48% and 77%). However, asenapine, at the doses tested, did not significantly alter D(3) binding in the brain regions examined in this study.These results indicate that asenapine has region-specific and dose-dependent effects on dopamine receptor subtypes in rat forebrain, which may contribute to asenapine's unique psychopharmacological properties. |
| Databáze: | OpenAIRE |
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