title: Lack of a role for the D3 receptor in clozapine induction of c-fos demonstrated in D3 dopamine receptor-deficient mice.
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.
authors.affiliation: Laboratory of Systems Neuroscience, National Institute of Mental Health, Bethesda, MD 20892, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Carta
authors.forename: C R
authors.initials: CR
authors.lastname: Gerfen
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D016762:Genes, fos / Q000235:genetics*; D051379:Mice; D009474:Neurons / Q000502:physiology; D009714:Nucleus Accumbens / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000172:deficiency* / Q000502:physiology*; D050637:Receptors, Dopamine D3
chemical_list: D014150:Antipsychotic Agents; C493594:Drd3 protein, mouse; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D003024:Clozapine