Dopamine receptor supersensitivity: development, mechanisms, presentation, and clinical applicability.

Area of Science:

• Neuroscience
• Pharmacology
• Neurobiology

Background:

• Receptor supersensitivity (RSS) is a known phenomenon following neuronal denervation.
• Dopamine receptor supersensitivity (DARSS) is implicated in various neuropsychiatric and neurodegenerative disorders.

Purpose of the Study:

• To elucidate the distinct mechanisms and circumstances underlying D1 and D2 dopamine receptor supersensitivity.
• To understand the differential induction and characteristics of D1 and D2 DARSS.

Main Methods:

• Studies involving perinatal destruction of nigrostriatal dopamine fibers in rodents.
• Administration of D1 and D2 dopamine agonists to intact and denervated rodent models.
• Observation of behavioral effects and receptor priming following agonist treatments.

Main Results:

• Overt D1 DARSS occurs after perinatal dopamine denervation, often requiring priming for maximal agonist effects.
• Perinatal dopamine denervation also induces serotonin (5-HT) RSS, which modulates D1 DARSS.
• D2 DARSS does not appear after perinatal dopamine denervation but results from repeated D2 agonist treatments in intact rats, leading to life-long supersensitivity.
• D1 and D2 DARSS are produced by different means, under different conditions, and may involve distinct neuronal phenotypes.

Conclusions:

• D1 and D2 DARSS are distinct processes with different etiological pathways and characteristics.
• Understanding these differences is crucial for addressing associated neuropsychiatric and neurodegenerative conditions.
• The findings suggest potential links between D2 DARSS and substance abuse.