RGD Reference Report - Differential regional and dose-related effects of asenapine on dopamine receptor subtypes. - Rat Genome Database

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Differential regional and dose-related effects of asenapine on dopamine receptor subtypes.

Authors: Tarazi, FI  Moran-Gates, T  Wong, EH  Henry, B  Shahid, M 
Citation: Tarazi FI, etal., Psychopharmacology (Berl). 2008 May;198(1):103-11. Epub 2008 Feb 24.
RGD ID: 2311562
Pubmed: PMID:18297468   (View Abstract at PubMed)
DOI: DOI:10.1007/s00213-008-1098-7   (Journal Full-text)

RATIONALE: The novel psychopharmacologic agent, asenapine, has high affinity for a range of receptors including the dopaminergic receptors. OBJECTIVE: 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). METHODS: 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). RESULTS: Four weeks of asenapine at 0.3 mg/kg significantly (P < 0.05) 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 (P < 0.05) 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. CONCLUSIONS: 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.

Objects referenced in this article
Gene Drd2 dopamine receptor D2 Rattus norvegicus

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