Rotation and striatal c-fos expression after repeated, daily treatment with selective dopamine receptor agonists and...

Area of Science:

• Neuroscience
• Pharmacology
• Neurobiology

Background:

• Daily injections of dopamine (DA) D2 receptor agonists typically induce behavioral sensitization in DA-depleted rats.
• Effects of repeated selective DA D1 receptor agonist treatment are less clear, showing equivocal results.
• Understanding differential D1/D2 receptor agonist effects is crucial for Parkinson's disease and related disorders.

Purpose of the Study:

• To investigate the effects of acute and repeated DA receptor agonist treatments with varying D1/D2 selectivities.
• To assess behavioral responses (rotation) and striatal c-fos activation in unilaterally DA-depleted rats.
• To elucidate the roles of D1 and D2 receptors in drug-induced behavioral changes and neuroadaptations.

Main Methods:

• Rats with unilateral DA depletions received daily treatments for 10 days.
• Treatments included a selective D1 agonist (A-85653), a D2 agonist (quinpirole), a combination, or levodopa (L-DOPA).
• Behavioral rotation and striatal c-fos expression were quantified to assess drug effects.

Main Results:

• A-85653 alone led to behavioral tolerance with repeated administration.
• Quinpirole or L-DOPA alone resulted in behavioral sensitization.
• Combined A-85653 + quinpirole showed increased response magnitude but reduced duration; c-fos activation decreased with repeated treatments despite enhanced rotation for quinpirole + A-85653 and L-DOPA.

Conclusions:

• Repeated D1 receptor stimulation may lead to desensitization.
• Behavioral sensitization from repeated L-DOPA treatment appears to be primarily mediated by the D2 receptor.
• Differential receptor desensitization underlies varied responses to dopaminergic therapies.