Relationship between asymmetries in striatal dopamine release and the direction of amphetamine‐induced rotation during. The first week following a unilateral 6‐OHDA lesion of the substantia nigra

Relationship between asymmetries in striatal dopamine release and the direction of... In animals with a large unilateral 6‐hydroxydopamine (6‐OHDA) lesion of the nigrostriatal dopamine (DA) system the traditional “rotational behavior model” states that amphetamine will induce circling behavior towards the denervated striatum (ipsiversive), that is, away from the side where there is greater amphetamine‐stimulated DA release and greater DA receptor stimulation. It is puzzling, therefore, why amphetamine induces contraversive rotation in rats tested 4 days after a unilateral 6‐OHDA lesion, despite a 90‐95% loss of the dopaminergic input to the striatum by this time. Rats reverse their direction of amphetamine‐induced rotation by 8 days post‐lesion and turn in the ipsiversive direction thereafter. To try and resolve this paradox, bilateral striatal microdialysis was used to estimate the effects of amphetamine on DA neurotransmission on Day 4 and Day 8 following a large unilateral 6‐OHDA lesion of the substantia nigra. On Day 4 post‐lesion, amphetamine produced a moderate (around 50% of control) increase in the extracellular concentration of DA in the denervated striatum. This amphetamine‐releasable pool of DA was exhausted by a single amphetamine challenge, because a second injection of amphetamine given 3 h after the first did not produce a comparable increase in DA. It is suggested that on Day 4 post‐lesion the amount of DA released by amphetamine in the denervated striatum is sufficient to produce greater DA receptor stimulation on that side, because of DA receptor supersensitivity, and this leads to contraversive rotation. On Day 8 post‐lesion, amphetamine induced DA release in the intact striatum but had no effect on extracellular DA in the denervated striatum (DA was nondetectable). On Day 8, therefore, DA receptor stimulation would be greatest in the intact striatum, leading to ipsiversive rotation. In conclusion, it is suggested that the seemingly paradoxical reversal in the direction of amphetamine‐induced rotation that occurs over the first week following a unilateral 6‐OHDA lesion is consistent with the traditional rotational model, and is due to time‐dependent changes in the ability of amphetamine to release DA in the denervated striatum. © 1994 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Synapse Wiley

Relationship between asymmetries in striatal dopamine release and the direction of amphetamine‐induced rotation during. The first week following a unilateral 6‐OHDA lesion of the substantia nigra

Loading next page...
 
/lp/wiley/relationship-between-asymmetries-in-striatal-dopamine-release-and-the-U4bNZhl0Ie
Publisher
Wiley
Copyright
Copyright © 1994 Wiley‐Liss, Inc.
ISSN
0887-4476
eISSN
1098-2396
D.O.I.
10.1002/syn.890170103
Publisher site
See Article on Publisher Site

Abstract

In animals with a large unilateral 6‐hydroxydopamine (6‐OHDA) lesion of the nigrostriatal dopamine (DA) system the traditional “rotational behavior model” states that amphetamine will induce circling behavior towards the denervated striatum (ipsiversive), that is, away from the side where there is greater amphetamine‐stimulated DA release and greater DA receptor stimulation. It is puzzling, therefore, why amphetamine induces contraversive rotation in rats tested 4 days after a unilateral 6‐OHDA lesion, despite a 90‐95% loss of the dopaminergic input to the striatum by this time. Rats reverse their direction of amphetamine‐induced rotation by 8 days post‐lesion and turn in the ipsiversive direction thereafter. To try and resolve this paradox, bilateral striatal microdialysis was used to estimate the effects of amphetamine on DA neurotransmission on Day 4 and Day 8 following a large unilateral 6‐OHDA lesion of the substantia nigra. On Day 4 post‐lesion, amphetamine produced a moderate (around 50% of control) increase in the extracellular concentration of DA in the denervated striatum. This amphetamine‐releasable pool of DA was exhausted by a single amphetamine challenge, because a second injection of amphetamine given 3 h after the first did not produce a comparable increase in DA. It is suggested that on Day 4 post‐lesion the amount of DA released by amphetamine in the denervated striatum is sufficient to produce greater DA receptor stimulation on that side, because of DA receptor supersensitivity, and this leads to contraversive rotation. On Day 8 post‐lesion, amphetamine induced DA release in the intact striatum but had no effect on extracellular DA in the denervated striatum (DA was nondetectable). On Day 8, therefore, DA receptor stimulation would be greatest in the intact striatum, leading to ipsiversive rotation. In conclusion, it is suggested that the seemingly paradoxical reversal in the direction of amphetamine‐induced rotation that occurs over the first week following a unilateral 6‐OHDA lesion is consistent with the traditional rotational model, and is due to time‐dependent changes in the ability of amphetamine to release DA in the denervated striatum. © 1994 Wiley‐Liss, Inc.

Journal

SynapseWiley

Published: May 1, 1994

References

  • Time course of adaptations in dopamine biosynthesis, metabolism, and release following nigrostriatal lesions: Implications for behavioral recovery from brain injury
    Altar, Altar; Marien, Marien; Marshall, Marshall
  • Monitoring the stimulated release of dopamine with in vivo voltammetry. II. Clearance of released dopamine from extracellular fluid
    Ewing, Ewing; Wightman, Wightman
  • Ionic composition of microdialysis perfusing solution alters the pharmacological responsiveness and basal outflow of striatal dopamine
    Moghaddam, Moghaddam; Bunney, Bunney

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