Long‐Term Survival of Intrastriatal Dopaminergic Grafts: Modulation of Acetylcholine Release by Graft‐Derived Dopamine

Long‐Term Survival of Intrastriatal Dopaminergic Grafts: Modulation of Acetylcholine Release by... Abstract: The nigrostriatal dopaminergic system of rats was unilaterally lesioned with 6‐hydroxydopamine. Part of the animals was grafted 2 weeks later with fetal dopaminergic cells on the lesioned side; untreated rats of the same strain served as controls. Both 3 and 12–14 months after surgery the striatal dopamine (DA) content and the in vivo rotational response following injection of d‐amphetamine showed significant changes in grafted as compared to lesioned animals. At 12–14 months after transplantation, the electrically evoked release of tritiated DA and acetylcholine (ACh) in slices (preincubated with (3H)DA or (3H)choline, respectively) of striata of intact, lesioned, or grafted animals was also investigated. Electrical field stimulation of striatal slices of the lesioned side did not evoke any significant (3H)DA overflow, whereas a marked (3H)DA release was observed in slices of grafted and control striata. Moreover, both DL‐amphetamine (3 μM) and nomifensine (10μM) strongly enhanced basal 3H outflow in these slices. Electrically evoked (3H)ACh release was significantly reduced in slices from all striatal tissues by 0.01 μM apomorphine. In slices from denervated striata a clearcut hypersensitivity for this action of apomorphine was present, indicating super sensitivity of DA receptors on cholinergic terminals; this hypersensitivity was significantly reduced in graft‐bearing striata. Furthermore, because this hypersensitivity was unchanged in slices of lesioned striata under stimulation conditions (four pulses/100 Hz) avoiding inhibition by endogenously released DA, it is concluded that lesion‐induced DA receptor super sensitivity is caused by an increase in receptor density or efficacy rather than by a decreased competition between endogenous and exogenous agonists. Both reuptake blockade of DA with nomifensine (10 μM) and release of endogenous DA by DL‐amphetamine (3 μM) potently reduced (3H)ACh release only in control and grafted but not in lesioned tissue. In experiments using potassium‐evoked (3H)ACh release, tetrodotoxin had no effect on the inhibitory activity of amphetamine and nomifensine, indicating that the DA receptors involved in their indirect inhibitory action are located directly on the cholinergic terminals. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

Long‐Term Survival of Intrastriatal Dopaminergic Grafts: Modulation of Acetylcholine Release by Graft‐Derived Dopamine

Loading next page...
 
/lp/wiley/long-term-survival-of-intrastriatal-dopaminergic-grafts-modulation-of-3Z4IwLZZlR
Publisher
Wiley
Copyright
Copyright © 1991 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3042
eISSN
1471-4159
D.O.I.
10.1111/j.1471-4159.1991.tb02124.x
Publisher site
See Article on Publisher Site

Abstract

Abstract: The nigrostriatal dopaminergic system of rats was unilaterally lesioned with 6‐hydroxydopamine. Part of the animals was grafted 2 weeks later with fetal dopaminergic cells on the lesioned side; untreated rats of the same strain served as controls. Both 3 and 12–14 months after surgery the striatal dopamine (DA) content and the in vivo rotational response following injection of d‐amphetamine showed significant changes in grafted as compared to lesioned animals. At 12–14 months after transplantation, the electrically evoked release of tritiated DA and acetylcholine (ACh) in slices (preincubated with (3H)DA or (3H)choline, respectively) of striata of intact, lesioned, or grafted animals was also investigated. Electrical field stimulation of striatal slices of the lesioned side did not evoke any significant (3H)DA overflow, whereas a marked (3H)DA release was observed in slices of grafted and control striata. Moreover, both DL‐amphetamine (3 μM) and nomifensine (10μM) strongly enhanced basal 3H outflow in these slices. Electrically evoked (3H)ACh release was significantly reduced in slices from all striatal tissues by 0.01 μM apomorphine. In slices from denervated striata a clearcut hypersensitivity for this action of apomorphine was present, indicating super sensitivity of DA receptors on cholinergic terminals; this hypersensitivity was significantly reduced in graft‐bearing striata. Furthermore, because this hypersensitivity was unchanged in slices of lesioned striata under stimulation conditions (four pulses/100 Hz) avoiding inhibition by endogenously released DA, it is concluded that lesion‐induced DA receptor super sensitivity is caused by an increase in receptor density or efficacy rather than by a decreased competition between endogenous and exogenous agonists. Both reuptake blockade of DA with nomifensine (10 μM) and release of endogenous DA by DL‐amphetamine (3 μM) potently reduced (3H)ACh release only in control and grafted but not in lesioned tissue. In experiments using potassium‐evoked (3H)ACh release, tetrodotoxin had no effect on the inhibitory activity of amphetamine and nomifensine, indicating that the DA receptors involved in their indirect inhibitory action are located directly on the cholinergic terminals.

Journal

Journal of NeurochemistryWiley

Published: Jul 1, 1991

References

  • Inhibition of the electrically evoked release of ( 3 H)acetylcholine in rat striatal slices: an experimental model for drugs that enhance dopaminergic neurotransmission
    Baud, Baud; Arbilla, Arbilla; Langer, Langer
  • D 1 and D 2 dopaminergic regulation of acetylcholine release from striata of freely moving rats
    Bertorelli, Bertorelli; Consolo, Consolo
  • Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: immunological aspects, spontaneous and drug‐induced behaviour, and dopamine release
    Brundin, Brundin; Strecker, Strecker; Widner, Widner; Clarke, Clarke; Nilsson, Nilsson; Astedt, Astedt; Lindvall, Lindvall; Björklund, Björklund
  • Restoration of dopaminergic function by grafting of fetal rat substantia nigra to the caudate nucleus: long‐term behavioral, biochemical, and histochemical studies
    Freed, Freed; Perlow, Perlow; Karoum, Karoum; Seiger, Seiger; Olson, Olson; Hoffer, Hoffer; Wyatt, Wyatt
  • Intrastriatal dopaminergic grafts restore inhibitory control over striatal cholinergic neurons
    Herman, Herman; Lupp, Lupp; Abrous, Abrous; Moal, Moal; Hertting, Hertting; Jackisch, Jackisch
  • Functional activity of substantia nigra grafts reinnervating the striatum: neurotransmitter metabolism and ( 14 C)2‐deoxy‐d‐glucose autoradiography
    Schmidt, Schmidt; Ingvar, Ingvar; Lindvall, Lindvall; Stenevi, Stenevi; Björklund, Björklund

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off