Antisense oligodeoxynucleotide reduces brain dopamine D2 receptors: behavioral correlates

Area of Science:

• Neuroscience
• Molecular Biology
• Pharmacology

Background:

• Dopamine receptors, particularly D2, play crucial roles in motor control and behavior.
• Understanding the precise function of dopamine D2 receptors requires specific methods for their modulation.

Purpose of the Study:

• To investigate the efficacy of antisense oligodeoxynucleotides in selectively down-regulating dopamine D2 receptors in the rat brain.
• To assess the behavioral consequences of reduced dopamine D2 receptor density.

Main Methods:

• Intraventricular infusion of antisense oligodeoxynucleotides targeting rat dopamine D2 receptor mRNA.
• Homogenate binding assays and autoradiography to quantify receptor density.
• Assessment of locomotor activity and grooming behavior in response to receptor agonists and antisense treatment.

Main Results:

• Antisense treatment reduced striatal dopamine D2 receptors by approximately 50% and nucleus accumbens D2 receptors by over 70%.
• D1, muscarinic, and serotonin 5-HT2 receptors remained unaffected, confirming specificity.
• Dopamine D2 receptor agonist-induced locomotor activation was inhibited, while D1 agonist-induced grooming was unchanged.
• Antisense treatment led to catalepsy and reduced spontaneous locomotor activity.

Conclusions:

• Antisense oligodeoxynucleotides provide a specific and effective tool for reducing dopamine D2 receptor expression in vivo.
• Down-regulation of dopamine D2 receptors significantly impairs motor activity and induces catalepsy, highlighting their critical role in motor control.