Effects of acute nicotine on hemodynamics and binding of [11C]raclopride to dopamine D2,3 receptors in pig brain

Paul Cumming, Pedro Rosa-Neto, Hideaki Watanabe, Donald Smith, Dirk Bender, Paul B S Clarke, Albert Gjedde

Research output: Contribution to journalArticle

Abstract

Positive reinforcing properties of nicotine and the psychostimulants have been attributed to elevated dopamine release in the basal ganglia. It is well known that the specific binding of [11C]raclopride to dopamine D2,3 receptors in living striatum is reduced by cocaine and amphetamines, revealing increased competition between endogenous dopamine and [11C]raclopride for dopamine D2,3 receptors. However, the sensitivity of [11C]raclopride binding to nicotine-induced dopamine release is less well documented. In order to provide the basis for mapping effects of nicotine, we first optimized reference tissue methods for quantifying [11C]raclopride binding sites in striatum of living pigs (n = 16). In the same animals, the rate of cerebral blood flow (CBF) was mapped using [15O]water. Neither a low dose of nicotine (50 μ kg-1, iv) nor a high dose of nicotine (500 μg kg-1, iv) altered CBF in the pig brain, an important condition for calculating the binding of radioligands when using a reference tissue to estimate the free ligand concentration. The methods of Logan and of Lammertsma were compared using the cerebellum or the occipital cortex as reference tissues for calculating the binding potential (pB) of [11C]raclolpride in brain. Irrespective of the method used, the mean undrugged baseline pB in striatum (ca. 2.0) was significantly asymmetric, with highest binding in the left caudate and right putamen. Test-retest estimates of pB were stable. Subtraction of Logan pB maps revealed that the low dose of nicotine reduced the pB of [11C]raclopride by 10% in a cluster of voxels in the left anteroventral striatum, but this effect did not persist after correction for multiple comparisons. The high dose of nicotine (n = 9) acutely reduced pB by 10% bilaterally in the ventral striatum; 3 h after the high nicotine dose, the reductions had shifted dorsally and caudally into the caudate and putamen. Evidently, nicotine challenge enhances the competition between endogenous dopamine for [11C]raclopride binding sites with a complex temporal and spacial pattern in pig brain, initially presenting in the left ventral striatum.

Original languageEnglish (US)
Pages (from-to)1127-1136
Number of pages10
JournalNeuroImage
Volume19
Issue number3
DOIs
StatePublished - Jul 1 2003
Externally publishedYes

Fingerprint

Raclopride
Dopamine D2 Receptors
Nicotine
Swine
Hemodynamics
Brain
Dopamine
Cerebrovascular Circulation
Putamen
Binding Sites
Amphetamines
Occipital Lobe
Basal Ganglia
Cocaine
Cerebellum
Ligands

Keywords

  • CBF
  • Competition
  • D2
  • Dopamine
  • Nicotine
  • Parametric mapping
  • Raclopride
  • Receptors

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Neurology

Cite this

Cumming, P., Rosa-Neto, P., Watanabe, H., Smith, D., Bender, D., Clarke, P. B. S., & Gjedde, A. (2003). Effects of acute nicotine on hemodynamics and binding of [11C]raclopride to dopamine D2,3 receptors in pig brain. NeuroImage, 19(3), 1127-1136. https://doi.org/10.1016/S1053-8119(03)00079-X

Effects of acute nicotine on hemodynamics and binding of [11C]raclopride to dopamine D2,3 receptors in pig brain. / Cumming, Paul; Rosa-Neto, Pedro; Watanabe, Hideaki; Smith, Donald; Bender, Dirk; Clarke, Paul B S; Gjedde, Albert.

In: NeuroImage, Vol. 19, No. 3, 01.07.2003, p. 1127-1136.

Research output: Contribution to journalArticle

Cumming, P, Rosa-Neto, P, Watanabe, H, Smith, D, Bender, D, Clarke, PBS & Gjedde, A 2003, 'Effects of acute nicotine on hemodynamics and binding of [11C]raclopride to dopamine D2,3 receptors in pig brain', NeuroImage, vol. 19, no. 3, pp. 1127-1136. https://doi.org/10.1016/S1053-8119(03)00079-X
Cumming, Paul ; Rosa-Neto, Pedro ; Watanabe, Hideaki ; Smith, Donald ; Bender, Dirk ; Clarke, Paul B S ; Gjedde, Albert. / Effects of acute nicotine on hemodynamics and binding of [11C]raclopride to dopamine D2,3 receptors in pig brain. In: NeuroImage. 2003 ; Vol. 19, No. 3. pp. 1127-1136.
@article{ebc8903101b14b8c9a08464dad6da7aa,
title = "Effects of acute nicotine on hemodynamics and binding of [11C]raclopride to dopamine D2,3 receptors in pig brain",
abstract = "Positive reinforcing properties of nicotine and the psychostimulants have been attributed to elevated dopamine release in the basal ganglia. It is well known that the specific binding of [11C]raclopride to dopamine D2,3 receptors in living striatum is reduced by cocaine and amphetamines, revealing increased competition between endogenous dopamine and [11C]raclopride for dopamine D2,3 receptors. However, the sensitivity of [11C]raclopride binding to nicotine-induced dopamine release is less well documented. In order to provide the basis for mapping effects of nicotine, we first optimized reference tissue methods for quantifying [11C]raclopride binding sites in striatum of living pigs (n = 16). In the same animals, the rate of cerebral blood flow (CBF) was mapped using [15O]water. Neither a low dose of nicotine (50 μ kg-1, iv) nor a high dose of nicotine (500 μg kg-1, iv) altered CBF in the pig brain, an important condition for calculating the binding of radioligands when using a reference tissue to estimate the free ligand concentration. The methods of Logan and of Lammertsma were compared using the cerebellum or the occipital cortex as reference tissues for calculating the binding potential (pB) of [11C]raclolpride in brain. Irrespective of the method used, the mean undrugged baseline pB in striatum (ca. 2.0) was significantly asymmetric, with highest binding in the left caudate and right putamen. Test-retest estimates of pB were stable. Subtraction of Logan pB maps revealed that the low dose of nicotine reduced the pB of [11C]raclopride by 10{\%} in a cluster of voxels in the left anteroventral striatum, but this effect did not persist after correction for multiple comparisons. The high dose of nicotine (n = 9) acutely reduced pB by 10{\%} bilaterally in the ventral striatum; 3 h after the high nicotine dose, the reductions had shifted dorsally and caudally into the caudate and putamen. Evidently, nicotine challenge enhances the competition between endogenous dopamine for [11C]raclopride binding sites with a complex temporal and spacial pattern in pig brain, initially presenting in the left ventral striatum.",
keywords = "CBF, Competition, D2, Dopamine, Nicotine, Parametric mapping, Raclopride, Receptors",
author = "Paul Cumming and Pedro Rosa-Neto and Hideaki Watanabe and Donald Smith and Dirk Bender and Clarke, {Paul B S} and Albert Gjedde",
year = "2003",
month = "7",
day = "1",
doi = "10.1016/S1053-8119(03)00079-X",
language = "English (US)",
volume = "19",
pages = "1127--1136",
journal = "NeuroImage",
issn = "1053-8119",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Effects of acute nicotine on hemodynamics and binding of [11C]raclopride to dopamine D2,3 receptors in pig brain

AU - Cumming, Paul

AU - Rosa-Neto, Pedro

AU - Watanabe, Hideaki

AU - Smith, Donald

AU - Bender, Dirk

AU - Clarke, Paul B S

AU - Gjedde, Albert

PY - 2003/7/1

Y1 - 2003/7/1

N2 - Positive reinforcing properties of nicotine and the psychostimulants have been attributed to elevated dopamine release in the basal ganglia. It is well known that the specific binding of [11C]raclopride to dopamine D2,3 receptors in living striatum is reduced by cocaine and amphetamines, revealing increased competition between endogenous dopamine and [11C]raclopride for dopamine D2,3 receptors. However, the sensitivity of [11C]raclopride binding to nicotine-induced dopamine release is less well documented. In order to provide the basis for mapping effects of nicotine, we first optimized reference tissue methods for quantifying [11C]raclopride binding sites in striatum of living pigs (n = 16). In the same animals, the rate of cerebral blood flow (CBF) was mapped using [15O]water. Neither a low dose of nicotine (50 μ kg-1, iv) nor a high dose of nicotine (500 μg kg-1, iv) altered CBF in the pig brain, an important condition for calculating the binding of radioligands when using a reference tissue to estimate the free ligand concentration. The methods of Logan and of Lammertsma were compared using the cerebellum or the occipital cortex as reference tissues for calculating the binding potential (pB) of [11C]raclolpride in brain. Irrespective of the method used, the mean undrugged baseline pB in striatum (ca. 2.0) was significantly asymmetric, with highest binding in the left caudate and right putamen. Test-retest estimates of pB were stable. Subtraction of Logan pB maps revealed that the low dose of nicotine reduced the pB of [11C]raclopride by 10% in a cluster of voxels in the left anteroventral striatum, but this effect did not persist after correction for multiple comparisons. The high dose of nicotine (n = 9) acutely reduced pB by 10% bilaterally in the ventral striatum; 3 h after the high nicotine dose, the reductions had shifted dorsally and caudally into the caudate and putamen. Evidently, nicotine challenge enhances the competition between endogenous dopamine for [11C]raclopride binding sites with a complex temporal and spacial pattern in pig brain, initially presenting in the left ventral striatum.

AB - Positive reinforcing properties of nicotine and the psychostimulants have been attributed to elevated dopamine release in the basal ganglia. It is well known that the specific binding of [11C]raclopride to dopamine D2,3 receptors in living striatum is reduced by cocaine and amphetamines, revealing increased competition between endogenous dopamine and [11C]raclopride for dopamine D2,3 receptors. However, the sensitivity of [11C]raclopride binding to nicotine-induced dopamine release is less well documented. In order to provide the basis for mapping effects of nicotine, we first optimized reference tissue methods for quantifying [11C]raclopride binding sites in striatum of living pigs (n = 16). In the same animals, the rate of cerebral blood flow (CBF) was mapped using [15O]water. Neither a low dose of nicotine (50 μ kg-1, iv) nor a high dose of nicotine (500 μg kg-1, iv) altered CBF in the pig brain, an important condition for calculating the binding of radioligands when using a reference tissue to estimate the free ligand concentration. The methods of Logan and of Lammertsma were compared using the cerebellum or the occipital cortex as reference tissues for calculating the binding potential (pB) of [11C]raclolpride in brain. Irrespective of the method used, the mean undrugged baseline pB in striatum (ca. 2.0) was significantly asymmetric, with highest binding in the left caudate and right putamen. Test-retest estimates of pB were stable. Subtraction of Logan pB maps revealed that the low dose of nicotine reduced the pB of [11C]raclopride by 10% in a cluster of voxels in the left anteroventral striatum, but this effect did not persist after correction for multiple comparisons. The high dose of nicotine (n = 9) acutely reduced pB by 10% bilaterally in the ventral striatum; 3 h after the high nicotine dose, the reductions had shifted dorsally and caudally into the caudate and putamen. Evidently, nicotine challenge enhances the competition between endogenous dopamine for [11C]raclopride binding sites with a complex temporal and spacial pattern in pig brain, initially presenting in the left ventral striatum.

KW - CBF

KW - Competition

KW - D2

KW - Dopamine

KW - Nicotine

KW - Parametric mapping

KW - Raclopride

KW - Receptors

UR - http://www.scopus.com/inward/record.url?scp=0038348513&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038348513&partnerID=8YFLogxK

U2 - 10.1016/S1053-8119(03)00079-X

DO - 10.1016/S1053-8119(03)00079-X

M3 - Article

VL - 19

SP - 1127

EP - 1136

JO - NeuroImage

JF - NeuroImage

SN - 1053-8119

IS - 3

ER -