Functional recovery of supersensitive dopamine receptors after intrastriatal grafts of fetal substantia nigra

Ted M Dawson, Valina Dawson, Fred H. Gage, Lisa J. Fisher, Mary A. Hunt, James K. Wamsley

Research output: Contribution to journalArticle

Abstract

Interruption of the ascending dopamine neurons of the nigrostriatal pathway, by 6-hydroxydopamine (6-OHDA) lesion in rats, produced a significant loss of the dopamine transport complexes labeled with the phencyclidine derivative [3H]BTCP. This loss of dopamine innervation in the striatum was present at least 12 to 14 months after lesioning and was functionally manifested by ipsilateral rotation of the animals in response to amphetamine. In these same animals, in comparison to controls, there was a significant increase in the number (Bmax) of [3H]SCH 23390-labeled D-1 receptors in the striatum (36.7%) and the substantia nigra (35.1%) and a 54.4% increase in the number (Bmax) of [3H]sulpiride-labeled striatal D-2 receptors without an apparent change in affinity (Kd). Ten to twelve months after the transplantation of homologous fetal substantia nigra into the denervated striatum, there was a significant decrease in amphetamine-induced turning behavior. In these animals, there was an ingrowth of dopamine nerve terminals in the striatum as demonstrated by a return of [3H]BTCP binding. Accompanying this reinnervation was the normalization of D-1 and D-2 receptors to control values in the striatum as well as the return of D-1 receptors to prelesion densities in the substantia nigra. In a subgroup of transplanted rats, amphetamine continued to induce ipsilateral turning. In these animals both D-1 and D-2 receptors remained supersensitive. These results support the hypothesis that the functional recovery of transplanted animals is due, in part, to reinnervation of the striatum. In addition, long-term alterations in receptor density may be related to the behavioral deficits that are associated with the 6-OHDA-lesioned rat. Furthermore, dopamine receptor plasticity may play a role in the functional recovery of substantia nigra transplanted animals and graft viability seems to be a prerequisite for behavioral recovery as well as receptor normalization.

Original languageEnglish (US)
Pages (from-to)282-292
Number of pages11
JournalExperimental Neurology
Volume111
Issue number3
DOIs
StatePublished - 1991
Externally publishedYes

Fingerprint

Dopamine Receptors
Substantia Nigra
Transplants
Oxidopamine
Amphetamine
Dopamine
Corpus Striatum
Phencyclidine
Sulpiride
Dopaminergic Neurons
Homologous Transplantation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Neurology

Cite this

Functional recovery of supersensitive dopamine receptors after intrastriatal grafts of fetal substantia nigra. / Dawson, Ted M; Dawson, Valina; Gage, Fred H.; Fisher, Lisa J.; Hunt, Mary A.; Wamsley, James K.

In: Experimental Neurology, Vol. 111, No. 3, 1991, p. 282-292.

Research output: Contribution to journalArticle

Dawson, Ted M ; Dawson, Valina ; Gage, Fred H. ; Fisher, Lisa J. ; Hunt, Mary A. ; Wamsley, James K. / Functional recovery of supersensitive dopamine receptors after intrastriatal grafts of fetal substantia nigra. In: Experimental Neurology. 1991 ; Vol. 111, No. 3. pp. 282-292.
@article{833abc55bf9446378b8df87fd870de61,
title = "Functional recovery of supersensitive dopamine receptors after intrastriatal grafts of fetal substantia nigra",
abstract = "Interruption of the ascending dopamine neurons of the nigrostriatal pathway, by 6-hydroxydopamine (6-OHDA) lesion in rats, produced a significant loss of the dopamine transport complexes labeled with the phencyclidine derivative [3H]BTCP. This loss of dopamine innervation in the striatum was present at least 12 to 14 months after lesioning and was functionally manifested by ipsilateral rotation of the animals in response to amphetamine. In these same animals, in comparison to controls, there was a significant increase in the number (Bmax) of [3H]SCH 23390-labeled D-1 receptors in the striatum (36.7{\%}) and the substantia nigra (35.1{\%}) and a 54.4{\%} increase in the number (Bmax) of [3H]sulpiride-labeled striatal D-2 receptors without an apparent change in affinity (Kd). Ten to twelve months after the transplantation of homologous fetal substantia nigra into the denervated striatum, there was a significant decrease in amphetamine-induced turning behavior. In these animals, there was an ingrowth of dopamine nerve terminals in the striatum as demonstrated by a return of [3H]BTCP binding. Accompanying this reinnervation was the normalization of D-1 and D-2 receptors to control values in the striatum as well as the return of D-1 receptors to prelesion densities in the substantia nigra. In a subgroup of transplanted rats, amphetamine continued to induce ipsilateral turning. In these animals both D-1 and D-2 receptors remained supersensitive. These results support the hypothesis that the functional recovery of transplanted animals is due, in part, to reinnervation of the striatum. In addition, long-term alterations in receptor density may be related to the behavioral deficits that are associated with the 6-OHDA-lesioned rat. Furthermore, dopamine receptor plasticity may play a role in the functional recovery of substantia nigra transplanted animals and graft viability seems to be a prerequisite for behavioral recovery as well as receptor normalization.",
author = "Dawson, {Ted M} and Valina Dawson and Gage, {Fred H.} and Fisher, {Lisa J.} and Hunt, {Mary A.} and Wamsley, {James K.}",
year = "1991",
doi = "10.1016/0014-4886(91)90095-T",
language = "English (US)",
volume = "111",
pages = "282--292",
journal = "Experimental Neurology",
issn = "0014-4886",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Functional recovery of supersensitive dopamine receptors after intrastriatal grafts of fetal substantia nigra

AU - Dawson, Ted M

AU - Dawson, Valina

AU - Gage, Fred H.

AU - Fisher, Lisa J.

AU - Hunt, Mary A.

AU - Wamsley, James K.

PY - 1991

Y1 - 1991

N2 - Interruption of the ascending dopamine neurons of the nigrostriatal pathway, by 6-hydroxydopamine (6-OHDA) lesion in rats, produced a significant loss of the dopamine transport complexes labeled with the phencyclidine derivative [3H]BTCP. This loss of dopamine innervation in the striatum was present at least 12 to 14 months after lesioning and was functionally manifested by ipsilateral rotation of the animals in response to amphetamine. In these same animals, in comparison to controls, there was a significant increase in the number (Bmax) of [3H]SCH 23390-labeled D-1 receptors in the striatum (36.7%) and the substantia nigra (35.1%) and a 54.4% increase in the number (Bmax) of [3H]sulpiride-labeled striatal D-2 receptors without an apparent change in affinity (Kd). Ten to twelve months after the transplantation of homologous fetal substantia nigra into the denervated striatum, there was a significant decrease in amphetamine-induced turning behavior. In these animals, there was an ingrowth of dopamine nerve terminals in the striatum as demonstrated by a return of [3H]BTCP binding. Accompanying this reinnervation was the normalization of D-1 and D-2 receptors to control values in the striatum as well as the return of D-1 receptors to prelesion densities in the substantia nigra. In a subgroup of transplanted rats, amphetamine continued to induce ipsilateral turning. In these animals both D-1 and D-2 receptors remained supersensitive. These results support the hypothesis that the functional recovery of transplanted animals is due, in part, to reinnervation of the striatum. In addition, long-term alterations in receptor density may be related to the behavioral deficits that are associated with the 6-OHDA-lesioned rat. Furthermore, dopamine receptor plasticity may play a role in the functional recovery of substantia nigra transplanted animals and graft viability seems to be a prerequisite for behavioral recovery as well as receptor normalization.

AB - Interruption of the ascending dopamine neurons of the nigrostriatal pathway, by 6-hydroxydopamine (6-OHDA) lesion in rats, produced a significant loss of the dopamine transport complexes labeled with the phencyclidine derivative [3H]BTCP. This loss of dopamine innervation in the striatum was present at least 12 to 14 months after lesioning and was functionally manifested by ipsilateral rotation of the animals in response to amphetamine. In these same animals, in comparison to controls, there was a significant increase in the number (Bmax) of [3H]SCH 23390-labeled D-1 receptors in the striatum (36.7%) and the substantia nigra (35.1%) and a 54.4% increase in the number (Bmax) of [3H]sulpiride-labeled striatal D-2 receptors without an apparent change in affinity (Kd). Ten to twelve months after the transplantation of homologous fetal substantia nigra into the denervated striatum, there was a significant decrease in amphetamine-induced turning behavior. In these animals, there was an ingrowth of dopamine nerve terminals in the striatum as demonstrated by a return of [3H]BTCP binding. Accompanying this reinnervation was the normalization of D-1 and D-2 receptors to control values in the striatum as well as the return of D-1 receptors to prelesion densities in the substantia nigra. In a subgroup of transplanted rats, amphetamine continued to induce ipsilateral turning. In these animals both D-1 and D-2 receptors remained supersensitive. These results support the hypothesis that the functional recovery of transplanted animals is due, in part, to reinnervation of the striatum. In addition, long-term alterations in receptor density may be related to the behavioral deficits that are associated with the 6-OHDA-lesioned rat. Furthermore, dopamine receptor plasticity may play a role in the functional recovery of substantia nigra transplanted animals and graft viability seems to be a prerequisite for behavioral recovery as well as receptor normalization.

UR - http://www.scopus.com/inward/record.url?scp=0025980942&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025980942&partnerID=8YFLogxK

U2 - 10.1016/0014-4886(91)90095-T

DO - 10.1016/0014-4886(91)90095-T

M3 - Article

C2 - 1825638

AN - SCOPUS:0025980942

VL - 111

SP - 282

EP - 292

JO - Experimental Neurology

JF - Experimental Neurology

SN - 0014-4886

IS - 3

ER -