Pharmacological MRI response to a selective dopamine transporter inhibitor, GBR12909, in awake and anesthetized rats

Yuto Kashiwagi, Takemi Rokugawa, Tomomi Yamada, Atsushi Obata, Hiroshi Watabe, Yoshichika Yoshioka, Koji Abe

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Pharmacological magnetic resonance imaging (phMRI) is a powerful tool for imaging the effects of drugs on brain activity. In preclinical phMRI studies, general anesthesia used for minimizing head movements is thought to influence the phMRI responses to drugs. In this study we investigated the phMRI responses to a selective dopamine transporter (DAT) inhibitor, GBR12909, and a dopamine (DA) releaser, d-amphetamine (AMPH), in the isoflurane anesthetized and awake rats using a relative cerebral blood volume (rCBV) method. AMPH (1 mg/kg i.p.) caused an increase in rCBV in the dopaminergic circuitry in the both anesthetized and awake rats. The striatal rCBV change was correlated with the change of the striatal DA concentration induced by AMPH in the both anesthetized and awake rats. GBR12909 (10 mg/kg i.p.) caused a positive rCBV response and showed a similar regional pattern of rCBV response to AMPH in the awake rats, and the correlation between the change of the striatal rCBV and the striatal DA concentration was observed. However, in the anesthetized rats, GBR12909 induced a widespread negative rCBV response, whereas an increase in striatal DA concentration was observed. These findings indicate that phMRI responses to activation of DA neurotransmission by GBR12909 or AMPH are overall identical in the awake state, while the phMRI response to a DAT inhibitor, GBR12909 but not to AMPH was changed by isoflurane anesthesia. For the evaluation of neuroactive drugs using phMRI, isoflurane anesthesia might be complicated the interpretation of pharmacodynamic effects of drugs in preclinical studies.

Original languageEnglish
Pages (from-to)203-212
Number of pages10
JournalSynapse
Volume69
Issue number4
DOIs
Publication statusPublished - Apr 1 2015
Externally publishedYes

Fingerprint

Dopamine Plasma Membrane Transport Proteins
Dextroamphetamine
Corpus Striatum
Magnetic Resonance Imaging
Pharmacology
Dopamine
Isoflurane
Anesthesia
Pharmaceutical Preparations
Head Movements
Drug Evaluation
Cerebral Blood Volume
Synaptic Transmission
General Anesthesia
Brain

Keywords

  • DAT inhibitor
  • Dopamine
  • GBR12909
  • Isoflurane
  • Pharmacological MRI

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Pharmacological MRI response to a selective dopamine transporter inhibitor, GBR12909, in awake and anesthetized rats. / Kashiwagi, Yuto; Rokugawa, Takemi; Yamada, Tomomi; Obata, Atsushi; Watabe, Hiroshi; Yoshioka, Yoshichika; Abe, Koji.

In: Synapse, Vol. 69, No. 4, 01.04.2015, p. 203-212.

Research output: Contribution to journalArticle

Kashiwagi, Y, Rokugawa, T, Yamada, T, Obata, A, Watabe, H, Yoshioka, Y & Abe, K 2015, 'Pharmacological MRI response to a selective dopamine transporter inhibitor, GBR12909, in awake and anesthetized rats', Synapse, vol. 69, no. 4, pp. 203-212. https://doi.org/10.1002/syn.21803
Kashiwagi, Yuto ; Rokugawa, Takemi ; Yamada, Tomomi ; Obata, Atsushi ; Watabe, Hiroshi ; Yoshioka, Yoshichika ; Abe, Koji. / Pharmacological MRI response to a selective dopamine transporter inhibitor, GBR12909, in awake and anesthetized rats. In: Synapse. 2015 ; Vol. 69, No. 4. pp. 203-212.
@article{e2ab1b9ceef145fea5e9644b85f4e7b5,
title = "Pharmacological MRI response to a selective dopamine transporter inhibitor, GBR12909, in awake and anesthetized rats",
abstract = "Pharmacological magnetic resonance imaging (phMRI) is a powerful tool for imaging the effects of drugs on brain activity. In preclinical phMRI studies, general anesthesia used for minimizing head movements is thought to influence the phMRI responses to drugs. In this study we investigated the phMRI responses to a selective dopamine transporter (DAT) inhibitor, GBR12909, and a dopamine (DA) releaser, d-amphetamine (AMPH), in the isoflurane anesthetized and awake rats using a relative cerebral blood volume (rCBV) method. AMPH (1 mg/kg i.p.) caused an increase in rCBV in the dopaminergic circuitry in the both anesthetized and awake rats. The striatal rCBV change was correlated with the change of the striatal DA concentration induced by AMPH in the both anesthetized and awake rats. GBR12909 (10 mg/kg i.p.) caused a positive rCBV response and showed a similar regional pattern of rCBV response to AMPH in the awake rats, and the correlation between the change of the striatal rCBV and the striatal DA concentration was observed. However, in the anesthetized rats, GBR12909 induced a widespread negative rCBV response, whereas an increase in striatal DA concentration was observed. These findings indicate that phMRI responses to activation of DA neurotransmission by GBR12909 or AMPH are overall identical in the awake state, while the phMRI response to a DAT inhibitor, GBR12909 but not to AMPH was changed by isoflurane anesthesia. For the evaluation of neuroactive drugs using phMRI, isoflurane anesthesia might be complicated the interpretation of pharmacodynamic effects of drugs in preclinical studies.",
keywords = "DAT inhibitor, Dopamine, GBR12909, Isoflurane, Pharmacological MRI",
author = "Yuto Kashiwagi and Takemi Rokugawa and Tomomi Yamada and Atsushi Obata and Hiroshi Watabe and Yoshichika Yoshioka and Koji Abe",
year = "2015",
month = "4",
day = "1",
doi = "10.1002/syn.21803",
language = "English",
volume = "69",
pages = "203--212",
journal = "Synapse",
issn = "0887-4476",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Pharmacological MRI response to a selective dopamine transporter inhibitor, GBR12909, in awake and anesthetized rats

AU - Kashiwagi, Yuto

AU - Rokugawa, Takemi

AU - Yamada, Tomomi

AU - Obata, Atsushi

AU - Watabe, Hiroshi

AU - Yoshioka, Yoshichika

AU - Abe, Koji

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Pharmacological magnetic resonance imaging (phMRI) is a powerful tool for imaging the effects of drugs on brain activity. In preclinical phMRI studies, general anesthesia used for minimizing head movements is thought to influence the phMRI responses to drugs. In this study we investigated the phMRI responses to a selective dopamine transporter (DAT) inhibitor, GBR12909, and a dopamine (DA) releaser, d-amphetamine (AMPH), in the isoflurane anesthetized and awake rats using a relative cerebral blood volume (rCBV) method. AMPH (1 mg/kg i.p.) caused an increase in rCBV in the dopaminergic circuitry in the both anesthetized and awake rats. The striatal rCBV change was correlated with the change of the striatal DA concentration induced by AMPH in the both anesthetized and awake rats. GBR12909 (10 mg/kg i.p.) caused a positive rCBV response and showed a similar regional pattern of rCBV response to AMPH in the awake rats, and the correlation between the change of the striatal rCBV and the striatal DA concentration was observed. However, in the anesthetized rats, GBR12909 induced a widespread negative rCBV response, whereas an increase in striatal DA concentration was observed. These findings indicate that phMRI responses to activation of DA neurotransmission by GBR12909 or AMPH are overall identical in the awake state, while the phMRI response to a DAT inhibitor, GBR12909 but not to AMPH was changed by isoflurane anesthesia. For the evaluation of neuroactive drugs using phMRI, isoflurane anesthesia might be complicated the interpretation of pharmacodynamic effects of drugs in preclinical studies.

AB - Pharmacological magnetic resonance imaging (phMRI) is a powerful tool for imaging the effects of drugs on brain activity. In preclinical phMRI studies, general anesthesia used for minimizing head movements is thought to influence the phMRI responses to drugs. In this study we investigated the phMRI responses to a selective dopamine transporter (DAT) inhibitor, GBR12909, and a dopamine (DA) releaser, d-amphetamine (AMPH), in the isoflurane anesthetized and awake rats using a relative cerebral blood volume (rCBV) method. AMPH (1 mg/kg i.p.) caused an increase in rCBV in the dopaminergic circuitry in the both anesthetized and awake rats. The striatal rCBV change was correlated with the change of the striatal DA concentration induced by AMPH in the both anesthetized and awake rats. GBR12909 (10 mg/kg i.p.) caused a positive rCBV response and showed a similar regional pattern of rCBV response to AMPH in the awake rats, and the correlation between the change of the striatal rCBV and the striatal DA concentration was observed. However, in the anesthetized rats, GBR12909 induced a widespread negative rCBV response, whereas an increase in striatal DA concentration was observed. These findings indicate that phMRI responses to activation of DA neurotransmission by GBR12909 or AMPH are overall identical in the awake state, while the phMRI response to a DAT inhibitor, GBR12909 but not to AMPH was changed by isoflurane anesthesia. For the evaluation of neuroactive drugs using phMRI, isoflurane anesthesia might be complicated the interpretation of pharmacodynamic effects of drugs in preclinical studies.

KW - DAT inhibitor

KW - Dopamine

KW - GBR12909

KW - Isoflurane

KW - Pharmacological MRI

UR - http://www.scopus.com/inward/record.url?scp=84925348091&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925348091&partnerID=8YFLogxK

U2 - 10.1002/syn.21803

DO - 10.1002/syn.21803

M3 - Article

C2 - 25612063

AN - SCOPUS:84925348091

VL - 69

SP - 203

EP - 212

JO - Synapse

JF - Synapse

SN - 0887-4476

IS - 4

ER -