ISSN:
1460-9568
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
On the basis of anatomical and pharmacological evidence, we have proposed that D3 receptor antagonism plays a role in the mediation of clozapine-, but not haloperidol-, induced immediate-early gene expression in the striatum. To test this hypothesis directly, we compared the effects of repeated administration of vehicle (8 mL/kg/day), clozapine (20 mg/kg/day) and haloperidol (2 mg/kg/day) for 17 days on expression of ΔFosB-like immunoreactivity (ΔFosB-Ir) in the island of Calleja major, nucleus accumbens and caudate-putamen of wild-type C57Bl6 (WT) and D3 receptor knockout (D3KO) mice. In vehicle-treated mice, the number of ΔFosB-Ir neurons in the nucleus accumbens was greater in D3KO than in WT mice. This finding is consistent with results implicating D3 receptor activation in the tonic inhibition of this limbic structure. Unlike rats, clozapine significantly increased the number of ΔFosB-Ir neurons in both the nucleus accumbens and the caudate-putamen of WT mice albeit to a lesser extent in the caudate-putamen than nucleus accumbens. Similar to rats, however, ΔFosB-Ir in the island of Calleja major of WT mice was elevated by clozapine but not by haloperidol. In the nucleus accumbens and caudate-putamen, haloperidol produced similar increases in ΔFosB-Ir in WT and D3KO mice. By contrast, clozapine-induced increases in ΔFosB-Ir in the island of Calleja major, nucleus accumbens and caudate-putamen of WT mice were absent in D3KO mice. These findings, which indicate that D3 receptor blockade is essential for clozapine-induced increases in striatal ΔFosB-Ir, suggest that D3 receptor antagonism may contribute to the unique therapeutic profile of this atypical antipsychotic.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1460-9568.2004.03774.x
Permalink
