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Up-regulation of D3 dopamine receptor mRNA by neuroleptics
1Genetic Pharmacology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1406, USA.
Abstract:
The effects of 14 days neuroleptic treatment on the expression of the D3 dopamine receptor gene was investigated in rats using a sensitive polymerase chain reaction assay. In olfactory tubercle, D3 mRNA levels increased following haloperidol (40%), pimozide (56%), and sulpiride (63%) administration, and in nucleus accumbens, levels increased after haloperidol (50%) and sulpiride (50%). D3 expression in the motor striatum did not change with any antagonist tested. Clozapine did not affect D3 expression in any brain region. These data suggest that dopamine antagonists can regulate the expression of the D3 receptor in a brain region selective manner. The findings also suggest that the motor complications of chronic antipsychotic therapy are not due to D3 receptor up-regulation in the striatum.
Insights
Neuroleptic drugs increase dopamine D3 receptor gene expression in specific rat brain regions, but not the motor striatum. This suggests antipsychotic side effects are not linked to D3 receptor changes in the striatum.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- The D3 dopamine receptor is a key target for antipsychotic medications.
- Understanding how neuroleptics affect D3 receptor gene expression is crucial for explaining treatment efficacy and side effects.
Purpose of the Study:
- To investigate the impact of 14-day neuroleptic treatment on D3 dopamine receptor gene expression in rat brain regions.
- To determine if D3 receptor upregulation in the striatum contributes to motor complications of antipsychotic therapy.
Main Methods:
- Utilized a sensitive polymerase chain reaction (PCR) assay to quantify D3 mRNA levels.
- Administered haloperidol, pimozide, sulpiride, and clozapine to rats for 14 days.
- Analyzed D3 expression in olfactory tubercle, nucleus accumbens, and motor striatum.
Main Results:
- Haloperidol, pimozide, and sulpiride increased D3 mRNA in the olfactory tubercle (40-63%).
- Haloperidol and sulpiride elevated D3 mRNA in the nucleus accumbens (50%).
- No significant changes in D3 expression were observed in the motor striatum with any tested antagonist.
- Clozapine did not alter D3 expression in any brain region examined.
Conclusions:
- Dopamine antagonists differentially regulate D3 receptor expression in a region-specific manner.
- The findings indicate that motor complications associated with antipsychotic treatment are unlikely to result from striatal D3 receptor upregulation.