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Decrease of behavioral and biochemical denervation supersensitivity of rat striatum by nigral transplants.

L Rioux1, D P Gaudin, C Gagnon

  • 1Department of Anatomy, Laval University, Québec, Canada.

Neuroscience
|January 1, 1991
PubMed
Summary

Fetal mesencephalic transplants in rats reduced dopamine receptor supersensitivity, particularly D2 receptors. This normalization of dopamine receptors improved behavioral responses to certain drugs after nigrostriatal pathway lesions.

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Area of Science:

  • Neuroscience
  • Neurobiology
  • Regenerative Medicine

Background:

  • Unilateral lesions of the nigrostriatal pathway in rats lead to dopamine receptor supersensitivity.
  • Fetal mesencephalic transplants are investigated as a potential therapy for dopamine-related disorders.

Purpose of the Study:

  • To investigate the effect of fetal mesencephalic transplants on dopamine receptor supersensitivity in a rat model of Parkinson's disease.
  • To assess the behavioral and biochemical changes following transplantation.

Main Methods:

  • Rats with unilateral 6-hydroxydopamine lesions of the substantia nigra received fetal mesencephalic transplants.
  • Behavioral testing included responses to apomorphine, amphetamine, D1 agonist (CY 208243), and D2 agonist (LY 171555).
  • Dopamine receptor density was quantified using autoradiography with [3H]SCH 23390 (D1) and [3H] spiperone (D2).

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Main Results:

  • Transplanted dopamine neurons reinnervated the striatum, increased dopamine levels, and reversed amphetamine-induced rotational asymmetry.
  • Apomorphine-induced circling was reduced post-transplant.
  • Circling evoked by D1 and D2 agonists was significantly less in grafted rats compared to controls.
  • Intrastriatal nigral transplants decreased D2 receptor supersensitivity and, to a lesser extent, D1 receptor supersensitivity.

Conclusions:

  • Fetal mesencephalic transplants can normalize dopamine receptor supersensitivity in lesioned rats.
  • Normalization of D2 receptors likely explains the reduced behavioral supersensitivity observed.
  • D1 receptors were less affected by the lesion and showed less normalization post-transplant.