A functional dissociation of the anterior and posterior pedunculopontine tegmental nucleus: excitotoxic lesions have differential effects on locomotion and the response to nicotine

Helen L Alderson, Mary P Latimer, Philip Winn

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Abstract

Excitotoxic lesions of posterior, but not anterior pedunculopontine tegmental nucleus (PPTg) change nicotine self-administration, consistent with the belief that the anterior PPTg (aPPTg) projects to substantia nigra pars compacta (SNC) and posterior PPTg (pPPTg) to the ventral tegmental area (VTA). The VTA is a likely site both of nicotine's reinforcing effect as well as its actions on locomotion. We hypothesized that pPPTg, but not aPPTg lesions, would alter locomotion in response to repeated nicotine administration by virtue of the fact that pPPTg appears to be more closely related to the VTA than is the aPPTg. Following excitotoxic lesions of aPPTg or pPPTg, rats were habituated to experimental procedures. Repeated (seven of each) nicotine (0.4 mg/kg) and saline injections were given following an on-off procedure. Measurement of spontaneous locomotion during habituation showed that aPPTg but not pPPTg lesioned rats were hypoactive relative to controls. Following nicotine, control rats showed locomotor depression for the first 2 days of treatment followed by enhanced locomotion relative to activity following saline treatment. Rats with aPPTg lesions showed a similar pattern, but the pPPTg lesioned rats showed no locomotor depression following nicotine treatment. These data confirm the role of the pPPTg in nicotine's behavioural effects--including the development of sensitization--and demonstrate for the first time that excitotoxic lesions of the aPPTg but not pPPTg generate a deficit in baseline activity. The finding that anterior but not posterior PPTg affects motor activity has significance for developing therapeutic strategies for Parkinsonism using deep brain stimulation aimed here.
LanguageEnglish
Pages247-253
Number of pages7
JournalBrain Structure and Function
Volume213
Issue number1-2
DOIs
Publication statusPublished - 2008

Fingerprint

Pedunculopontine Tegmental Nucleus
Locomotion
Nicotine
Ventral Tegmental Area
Deep Brain Stimulation
Self Administration
Parkinsonian Disorders
Therapeutics
Motor Activity
Injections

Keywords

  • analysis of variance
  • animals
  • excitatory amino acid agonists
  • ibotenic acid
  • microinjections
  • motor activity
  • nicotine
  • nicotinic agonists
  • pedunculopontine tegmental nucleus
  • rats

Cite this

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title = "A functional dissociation of the anterior and posterior pedunculopontine tegmental nucleus: excitotoxic lesions have differential effects on locomotion and the response to nicotine",
abstract = "Excitotoxic lesions of posterior, but not anterior pedunculopontine tegmental nucleus (PPTg) change nicotine self-administration, consistent with the belief that the anterior PPTg (aPPTg) projects to substantia nigra pars compacta (SNC) and posterior PPTg (pPPTg) to the ventral tegmental area (VTA). The VTA is a likely site both of nicotine's reinforcing effect as well as its actions on locomotion. We hypothesized that pPPTg, but not aPPTg lesions, would alter locomotion in response to repeated nicotine administration by virtue of the fact that pPPTg appears to be more closely related to the VTA than is the aPPTg. Following excitotoxic lesions of aPPTg or pPPTg, rats were habituated to experimental procedures. Repeated (seven of each) nicotine (0.4 mg/kg) and saline injections were given following an on-off procedure. Measurement of spontaneous locomotion during habituation showed that aPPTg but not pPPTg lesioned rats were hypoactive relative to controls. Following nicotine, control rats showed locomotor depression for the first 2 days of treatment followed by enhanced locomotion relative to activity following saline treatment. Rats with aPPTg lesions showed a similar pattern, but the pPPTg lesioned rats showed no locomotor depression following nicotine treatment. These data confirm the role of the pPPTg in nicotine's behavioural effects--including the development of sensitization--and demonstrate for the first time that excitotoxic lesions of the aPPTg but not pPPTg generate a deficit in baseline activity. The finding that anterior but not posterior PPTg affects motor activity has significance for developing therapeutic strategies for Parkinsonism using deep brain stimulation aimed here.",
keywords = "analysis of variance, animals, excitatory amino acid agonists, ibotenic acid, microinjections, motor activity , nicotine, nicotinic agonists, pedunculopontine tegmental nucleus, rats",
author = "Alderson, {Helen L} and Latimer, {Mary P} and Philip Winn",
year = "2008",
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T1 - A functional dissociation of the anterior and posterior pedunculopontine tegmental nucleus

T2 - Brain Structure and Function

AU - Alderson, Helen L

AU - Latimer, Mary P

AU - Winn, Philip

PY - 2008

Y1 - 2008

N2 - Excitotoxic lesions of posterior, but not anterior pedunculopontine tegmental nucleus (PPTg) change nicotine self-administration, consistent with the belief that the anterior PPTg (aPPTg) projects to substantia nigra pars compacta (SNC) and posterior PPTg (pPPTg) to the ventral tegmental area (VTA). The VTA is a likely site both of nicotine's reinforcing effect as well as its actions on locomotion. We hypothesized that pPPTg, but not aPPTg lesions, would alter locomotion in response to repeated nicotine administration by virtue of the fact that pPPTg appears to be more closely related to the VTA than is the aPPTg. Following excitotoxic lesions of aPPTg or pPPTg, rats were habituated to experimental procedures. Repeated (seven of each) nicotine (0.4 mg/kg) and saline injections were given following an on-off procedure. Measurement of spontaneous locomotion during habituation showed that aPPTg but not pPPTg lesioned rats were hypoactive relative to controls. Following nicotine, control rats showed locomotor depression for the first 2 days of treatment followed by enhanced locomotion relative to activity following saline treatment. Rats with aPPTg lesions showed a similar pattern, but the pPPTg lesioned rats showed no locomotor depression following nicotine treatment. These data confirm the role of the pPPTg in nicotine's behavioural effects--including the development of sensitization--and demonstrate for the first time that excitotoxic lesions of the aPPTg but not pPPTg generate a deficit in baseline activity. The finding that anterior but not posterior PPTg affects motor activity has significance for developing therapeutic strategies for Parkinsonism using deep brain stimulation aimed here.

AB - Excitotoxic lesions of posterior, but not anterior pedunculopontine tegmental nucleus (PPTg) change nicotine self-administration, consistent with the belief that the anterior PPTg (aPPTg) projects to substantia nigra pars compacta (SNC) and posterior PPTg (pPPTg) to the ventral tegmental area (VTA). The VTA is a likely site both of nicotine's reinforcing effect as well as its actions on locomotion. We hypothesized that pPPTg, but not aPPTg lesions, would alter locomotion in response to repeated nicotine administration by virtue of the fact that pPPTg appears to be more closely related to the VTA than is the aPPTg. Following excitotoxic lesions of aPPTg or pPPTg, rats were habituated to experimental procedures. Repeated (seven of each) nicotine (0.4 mg/kg) and saline injections were given following an on-off procedure. Measurement of spontaneous locomotion during habituation showed that aPPTg but not pPPTg lesioned rats were hypoactive relative to controls. Following nicotine, control rats showed locomotor depression for the first 2 days of treatment followed by enhanced locomotion relative to activity following saline treatment. Rats with aPPTg lesions showed a similar pattern, but the pPPTg lesioned rats showed no locomotor depression following nicotine treatment. These data confirm the role of the pPPTg in nicotine's behavioural effects--including the development of sensitization--and demonstrate for the first time that excitotoxic lesions of the aPPTg but not pPPTg generate a deficit in baseline activity. The finding that anterior but not posterior PPTg affects motor activity has significance for developing therapeutic strategies for Parkinsonism using deep brain stimulation aimed here.

KW - analysis of variance

KW - animals

KW - excitatory amino acid agonists

KW - ibotenic acid

KW - microinjections

KW - motor activity

KW - nicotine

KW - nicotinic agonists

KW - pedunculopontine tegmental nucleus

KW - rats

U2 - 10.1007/s00429-008-0174-4

DO - 10.1007/s00429-008-0174-4

M3 - Article

VL - 213

SP - 247

EP - 253

JO - Brain Structure and Function

JF - Brain Structure and Function

SN - 1863-2653

IS - 1-2

ER -