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Lack of effect of chronic dopamine receptor blockade on D2 dopamine receptor mRNA level
H H van Tol1, M Riva, O Civelli
1Center for Molecular and Behavioral Neuroscience, Rutgers, State University of New Jersey, Newark 07102.
Abstract:
The chronic treatment of rats with antipsychotic drugs which increase striatal D2 dopamine receptors did not measurably increase the level of D2 receptor mRNA indicating that the observed increase in receptors was not primarily due to transcriptional regulation. These and other data suggest that the molecular mechanisms involved in receptor regulation in response to denervation or neurotransmitter depletion may be different from those which occur in response to chronic receptor blockade by antagonist drugs.
Insights
Chronic antipsychotic drug treatment in rats increased dopamine D2 receptors without increasing their mRNA levels. This suggests receptor regulation occurs via non-transcriptional mechanisms, differing from denervation responses.
Area of Science:
- Neuropharmacology
- Molecular Neuroscience
- Receptor Biology
Background:
- Antipsychotic drugs are widely used to treat psychiatric disorders.
- These drugs are known to affect dopamine receptor systems, particularly the D2 dopamine receptor.
- Understanding the regulation of dopamine receptors is crucial for developing more effective treatments.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the increase in striatal D2 dopamine receptors following chronic antipsychotic drug treatment.
- To determine if transcriptional regulation plays a primary role in this receptor upregulation.
- To compare receptor regulation mechanisms induced by drug blockade versus denervation or neurotransmitter depletion.
Main Methods:
- Rats were chronically treated with antipsychotic drugs known to upregulate striatal D2 dopamine receptors.
- Levels of D2 receptor mRNA were measured to assess transcriptional activity.
- Receptor levels were quantified and compared between treated and control groups.
Main Results:
- Chronic antipsychotic treatment led to an increase in striatal D2 dopamine receptors.
- No significant increase in the level of D2 receptor mRNA was observed in treated rats.
- This indicates that the upregulation of D2 receptors was not primarily driven by increased gene transcription.
Conclusions:
- The upregulation of striatal D2 dopamine receptors by chronic antipsychotic drugs likely occurs through post-transcriptional or translational mechanisms.
- Molecular mechanisms for receptor regulation differ between chronic antagonist blockade and conditions like denervation or neurotransmitter depletion.
- These findings have implications for understanding antipsychotic drug action and receptor plasticity.