Excitotoxic lesions of the pedunculopontine tegmental nucleus of the rat. II. Examination of eating and drinking, rotation, and reaching and grasping following unilateral ibotenate or quinolinate lesions

J. S. Dunbar, K. Hitchcock, M. Latimer, E. L. Rugg, N. Ward, P. Winn

Research output: Contribution to journalArticle

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Abstract

The pedunculopontine tegmental nucleus (PPTg) contains a population of cholinergic neurons thought to be part of the ascending reticular activating system, and non-cholinergic neurons. In the previous study it was shown that various excitotoxins made effective lesions of cholinergic neurons in the PPTg but that quinolinate made smaller lesions in the non-cholinergic population, making it more selective than any other excitotoxin. The purpose of the present experiment was, first, to make lesions of cholinergic neurons throughout the length of the PPTg by infusing toxin at two different sites within it; and second, to examine simple motor activities in rats bearing either quinolinate or ibotenate lesions of the PPTg, and contrast these with the deficits seen after 6-hydroxydopamine (6-OHDA) induced lesions of mesostriatal dopamine (DA)-containing neurons. Post-mortem examination was carried out using choline acetyltransferase (ChAT) and tyrosine hydroxylase (TOH) immunohistochemistry, and routine Nissl staining. Both quinolinate and ibotenate destroyed ∼ 75% of ChAT-positive neurons in the PPTg, but damage to non-cholinergic neurons (assessed by Nissl staining) was twice as great following ibotenate as quinolinate, 6-OHDA induced almost complete lesions of mesotraial DA neurons, assessed by TOH immunohistochemistry. DA depleted rats showed deficits in drinking and spilled more food in the first 2 weeks after surgery, and were unable to reach or grasp food pellets in the staircase test. They also showed strong ipsilateral turning in response to amphetamine and contralateral turning to apomorphine. Quinolinate lesioned rats had no eating or drinking impairment in the home cage but showed a reaching (though not grasping) disability in the staircase test. They had a mild ipsilateral bias following amphetamine. Ibotenate lesioned rats, despite having larger lesions than the quinolinate, showed no deficits in eating or drinking in the home cage, or reaching or grasping disabilities in the staircase test. They did have a mild contralateral bias in response to amphetamine. This dissociation of the effects of quinolinate and ibotenate lesions of the PPTg is consistent with the suggestion that the PPTg has two functionally distinct components, and is attributed to the differential lesion of non-cholinergic neurons by the two excitotoxins.

LanguageEnglish
Pages194-206
Number of pages13
JournalBrain Research
Volume589
Issue number2
DOIs
Publication statusPublished - 4 Sep 1992

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Pedunculopontine Tegmental Nucleus
Quinolinic Acid
Drinking
Eating
Cholinergic Neurons
Oxidopamine
Neurotoxins
Amphetamine
Neurons
Choline O-Acetyltransferase
Dopaminergic Neurons
Tyrosine 3-Monooxygenase
Immunohistochemistry
Staining and Labeling
Food
Apomorphine
Population
Autopsy
Dopamine
Motor Activity

Keywords

  • 6-hydroxytryptamine
  • choline acetyltransferase
  • drinking
  • eating
  • excitotoxin
  • immunohistochemistry
  • staircase test
  • substantia nigra
  • tyrosine hydroxylase
  • ibotenic acid
  • oxidopamine
  • quinolinic acid
  • tyrosine 3 monooxygenase
  • animal experiment
  • animal tissue
  • controlled study
  • neurotoxicity

Cite this

@article{26250143f57e4972ad4315855eb5de49,
title = "Excitotoxic lesions of the pedunculopontine tegmental nucleus of the rat. II. Examination of eating and drinking, rotation, and reaching and grasping following unilateral ibotenate or quinolinate lesions",
abstract = "The pedunculopontine tegmental nucleus (PPTg) contains a population of cholinergic neurons thought to be part of the ascending reticular activating system, and non-cholinergic neurons. In the previous study it was shown that various excitotoxins made effective lesions of cholinergic neurons in the PPTg but that quinolinate made smaller lesions in the non-cholinergic population, making it more selective than any other excitotoxin. The purpose of the present experiment was, first, to make lesions of cholinergic neurons throughout the length of the PPTg by infusing toxin at two different sites within it; and second, to examine simple motor activities in rats bearing either quinolinate or ibotenate lesions of the PPTg, and contrast these with the deficits seen after 6-hydroxydopamine (6-OHDA) induced lesions of mesostriatal dopamine (DA)-containing neurons. Post-mortem examination was carried out using choline acetyltransferase (ChAT) and tyrosine hydroxylase (TOH) immunohistochemistry, and routine Nissl staining. Both quinolinate and ibotenate destroyed ∼ 75{\%} of ChAT-positive neurons in the PPTg, but damage to non-cholinergic neurons (assessed by Nissl staining) was twice as great following ibotenate as quinolinate, 6-OHDA induced almost complete lesions of mesotraial DA neurons, assessed by TOH immunohistochemistry. DA depleted rats showed deficits in drinking and spilled more food in the first 2 weeks after surgery, and were unable to reach or grasp food pellets in the staircase test. They also showed strong ipsilateral turning in response to amphetamine and contralateral turning to apomorphine. Quinolinate lesioned rats had no eating or drinking impairment in the home cage but showed a reaching (though not grasping) disability in the staircase test. They had a mild ipsilateral bias following amphetamine. Ibotenate lesioned rats, despite having larger lesions than the quinolinate, showed no deficits in eating or drinking in the home cage, or reaching or grasping disabilities in the staircase test. They did have a mild contralateral bias in response to amphetamine. This dissociation of the effects of quinolinate and ibotenate lesions of the PPTg is consistent with the suggestion that the PPTg has two functionally distinct components, and is attributed to the differential lesion of non-cholinergic neurons by the two excitotoxins.",
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author = "Dunbar, {J. S.} and K. Hitchcock and M. Latimer and Rugg, {E. L.} and N. Ward and P. Winn",
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Excitotoxic lesions of the pedunculopontine tegmental nucleus of the rat. II. Examination of eating and drinking, rotation, and reaching and grasping following unilateral ibotenate or quinolinate lesions. / Dunbar, J. S.; Hitchcock, K.; Latimer, M.; Rugg, E. L.; Ward, N.; Winn, P.

In: Brain Research, Vol. 589, No. 2, 04.09.1992, p. 194-206.

Research output: Contribution to journalArticle

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T1 - Excitotoxic lesions of the pedunculopontine tegmental nucleus of the rat. II. Examination of eating and drinking, rotation, and reaching and grasping following unilateral ibotenate or quinolinate lesions

AU - Dunbar, J. S.

AU - Hitchcock, K.

AU - Latimer, M.

AU - Rugg, E. L.

AU - Ward, N.

AU - Winn, P.

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KW - animal experiment

KW - animal tissue

KW - controlled study

KW - neurotoxicity

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