Dopamine D2(High) receptors moderately elevated by bifeprunox and aripiprazole

Area of Science:

• Neuroscience
• Pharmacology

Background:

• Long-term antipsychotic use can lead to behavioral dopamine supersensitivity.
• Dopamine supersensitivity in rats is linked to elevated dopamine D2(High) receptors in striata.

Purpose of the Study:

• To investigate if short-term administration of partial dopamine D2 agonists (bifeprunox, aripiprazole) induces biochemical changes indicative of dopamine supersensitivity.
• To compare the potency and efficacy of bifeprunox and aripiprazole at dopamine D2 receptors.

Main Methods:

• Assessed dopamine D2 receptor binding affinity (K(i)) and D2(High) receptor percentages in rat striata and human cloned D2Long receptors.
• Administered bifeprunox (0.25 mg/kg/day) for 9 days and aripiprazole (1.5 mg/kg) for 7 days to rats via subcutaneous injection.

Main Results:

• Bifeprunox demonstrated higher potency and efficacy than aripiprazole at human cloned D2Long receptors.
• Both bifeprunox and aripiprazole significantly increased D2(High) receptors in rat striata without altering the total D2 receptor population.
• The observed increase in D2(High) receptors was less pronounced than that induced by previous D2 antagonist antipsychotics.

Conclusions:

• Short-term treatment with bifeprunox and aripiprazole induces biochemical changes suggesting dopamine supersensitivity by increasing D2(High) receptors.
• The magnitude of D2(High) receptor increase is smaller compared to D2 antagonist antipsychotics.
• Further studies are required to determine if long-term partial dopamine D2 agonist treatment results in behavioral dopamine supersensitivity.