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  • Title: Lack of a role for the D3 receptor in clozapine induction of c-fos demonstrated in D3 dopamine receptor-deficient mice.
    Author: Carta AR, Gerfen CR.
    Journal: Neuroscience; 1999 Mar; 90(3):1021-9. PubMed ID: 10218801.
    Abstract:
    The role of the D3 dopamine receptor in mediating the effects of clozapine was analysed using in situ hybridization histochemistry to measure the induction of the immediate early gene c-fos in different brain areas of mice lacking a functional D3 dopamine receptor compared to wild type mice. Clozapine treatment (15 and 30 mg/kg, s.c.) resulted in a dose-dependent pattern of induction of c-fos messenger RNA in the striatum, accumbens and septal area, with a non-significant increase in the prefrontal cortex. There was no difference detected in any of these areas in the level of induction between mice lacking the D3 receptor (D3-/-) and wild type (D3+/+). To determine which types of neurons in the striatum and accumbens displayed clozapine (30 mg/kg) induction of c-fos messenger RNA, a double-labeling experiment was performed using a radioactive c-fos messenger RNA probe and a digoxigenin-labeled enkephalin messenger RNA probe, the latter used as a marker of D2-containing neurons. Clozapine-induced c-fos was detected in 20% of enkephalin-positive striatal neurons and 15% of enkephalin-positive accumbens neurons, and in both areas in about 10% of enkephalin-negative, putative D1 neurons, in both D3+/+ and D3-/- mice. These results demonstrate that clozapine induction of c-fos messenger RNA is not dependent on the D3 dopamine receptor subtype in the striatum or nucleus accumbens.
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