Neurotoxicity Research

, Volume 14, Issue 2–3, pp 121–128 | Cite as

Dopamine receptor supersensitivity: Development, mechanisms, presentation, and clinical applicability

  • Richard M. Kostrzewa
  • John P. Kostrzewa
  • Russell W. Brown
  • Przemyslaw Nowak
  • Ryszard Brus


The process of receptor supersensitivity (RSS) has a long history and is an epiphenomenon of neuronal denervation. Dopamine (DA) RSS (DARSS) similarly occurs after DA-denervation, and this process is invoked in neuropsychiatric and neurodegenerative disorders. From studies largely over the past 25 years, much has been learned regarding DARSS. For example, overt D1 DARSS occurs after perinatal destruction of nigrostriatal DA fibers. However, following perinatal destruction of DA innervation, the mostprominent behavioral effects of a D1 agonist are observed after a series of D1 agonist treatments- a process known aspriming of D1DA receptors. Moreover, perinatal lesioning of DA fibers produces prominent serotonin (5-HT) RSS, and in fact 5-HT RSS appears to modulate D1 DA RSS. In rodents, receptor supersensitization by these means appears to be irreversible. In contrast to the observedD 1 DARSS, D2 DARSS apparently does not occur after perinatal DA denervation. Also, while repeated D1 agonist treatment of intact rats has no observable effect, repeated D2 agonist treatments, during or after the ontogenetic phase, produces prominent life-long D2 RSS. The process may have an association with substance abuse. Therefore, production of D1 and D2 DARSS occurs by different means and under different circumstances, and in association with perhaps different neuronal phenotypes, and with greater incidence in either intact (D2) or DA-lesioned counterparts (D1). The physiological consequence of RSS are multiple.


Receptor supersensitivity Dopamine Serotonin Priming Denervation 


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Copyright information

© Springer 2008

Authors and Affiliations

  • Richard M. Kostrzewa
    • 1
  • John P. Kostrzewa
    • 1
  • Russell W. Brown
    • 2
  • Przemyslaw Nowak
    • 3
  • Ryszard Brus
    • 3
  1. 1.Department of Pharmacology, Quillen College of MedicineEast Tennessee State UniversityJohnson CityUSA
  2. 2.Department of PsychologyEast Tennessee State UniversityJohnson CityUSA
  3. 3.Department of PharmacologyMedical University of SilesiaZabrzePoland

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