Abstract
Neuroleptic treatment of schizophrenia provides a reduction in psychotic episodes and is accompanied by unwanted extrapyramidal side effects. Clozapine is atypical in that it does not produce these side effects. Typical antipsychotics have high affinity for dopamine D2 receptors, whereas atypicals, such as Clozapine, have D4 selectivity. Location of mRNA in rat brain show that D2 message is highest in the nigrostriatal areas, whereas D4 is distributed in cortical and limbic regions. The D4 selectivity of Clozapine and mRNA location indicate that D4 receptor antagonism may provide antipsychotic efficacy without extrapyramidal side effects. This study identifies for the first time the D4 receptor protein in autoradiographic blocking studies with [3H]-YM-09151-2 ([3M]-YM), a D2, D3, and D4 ligand. Blocked studies demonstrated that Raclopride, a D2/D3 compound, and D4 selective compounds Clozapine and (+)Apomorphine showed inhibitions in similar brain regions of D2 and D4 mRNA distribution, respectively. The study also investigated [3H] - Raclopride ([3H]-RAC) autoradiography to further contrast D2 location from D4. [3H]-RAC showed similar binding in regions blocked by cold Raclopride in [3H]-YM autoradiography. These findings reveal that the D4 receptor is located in dopaminergic structures involved in cognition and emotional stability while avoiding extrapyramidal structures which affect motor functioning.
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Stratman, N., Lahti, R. Localization Of The Dopamine D4 Receptor In Rat Brain -- An Autoradiographic Study Using [3H]--YM 09151-2. Neuropsychopharmacol 11, 286 (1994). https://doi.org/10.1038/sj.npp.1380218
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DOI: https://doi.org/10.1038/sj.npp.1380218