Differential regional and dose-related effects of asenapine on dopamine receptor subtypes.
BACKGROUND
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.
Tarazi
Frank I
FI
Mailman Research Center, McLean Hospital, Harvard Medical School, Belmont, MA, USA. ftarazi@hms.harvard.edu
Moran-Gates
Taylor
T
Wong
Erik H F
EH
Henry
Brian
B
Shahid
Mohammed
M
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003986:Dibenzocycloheptenes; D004305:Dose-Response Relationship, Drug; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D050637:Receptors, Dopamine D3 / Q000187:drug effects; D050638:Receptors, Dopamine D4 / Q000187:drug effects
D014150:Antipsychotic Agents; D003986:Dibenzocycloheptenes; D006576:Heterocyclic Compounds, 4 or More Rings; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; C522667:asenapine