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Functional magnetic resonance imaging studies of opioid receptor-mediated modulation of noxious-evoked BOLD contrast in rats

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Abstract

Rationale

Functional magnetic resonance imaging (fMRI) in rats can non-invasively identify brain regions activated by physiological stimuli and the effects of pharmacological intervention on these responses.

Objectives

This study was conducted to investigate the effects of systemic administration of the μ-opioid receptor agonist morphine on whole brain functional signal intensity in anaesthetised rats; to investigate whether pre-treatment with the opioid receptor antagonist naloxone blocks the effects of morphine; to determine whether pre-treatment with morphine attenuates noxious-evoked changes in whole brain functional signal intensity.

Methods

Continuous whole brain fMRI scanning was used to study brain signal intensity prior to, and following, systemic administration of morphine (5 mg/kg, n=7), systemic administration of naloxone (1 mg/kg) and morphine (n=8). Effects of pre-treatment with saline (n=5) or morphine (5 mg/kg, n=5) on formalin (5%, intraplantar)-evoked changes in signal intensity were determined. Data were processed using SMP99 with fixed-effects analysis (p<0.05).

Results

Morphine produced significant positive bilateral increases in signal intensity in the cingulate cortex, amygdala, thalamus, hypothalamus and PAG (p<0.05), and these effects were blocked by naloxone. Intraplantar injection of formalin produced a significant positive increase in signal intensity in the cingulate cortex, somatosensory cortex, amygdala, thalamus, hypothalamus and PAG (p<0.05). Morphine attenuated formalin-evoked increases in signal intensity in the PAG, amygdala, hypothalamus and cingulate cortex.

Conclusion

Our data demonstrate that morphine modulates noxious-evoked changes in signal intensity in discrete brain regions. fMRI studies in rats are able to identify specific brain regions involved in the pharmacological modification of physiologically evoked changes in regional brain activation.

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Abbreviations

BOLD:

Blood oxygenation level dependent

Cingulate CTX:

Cingulate cortex

DlPAG:

Dorsal lateral periaqueductal grey

DmCPU:

Dorsal medial caudate putamen

fMRI:

Functional magnetic resonance imaging

HindSSCTX:

Hindlimb area of somatosensory cortex

Lhypo:

Lateral hypothalamus

MR:

Magnetic resonance

MAP:

Mean arterial blood pressure

RARE:

Rapid acquisition relaxation enhanced

rCBF:

Regional cerebral bloodflow

RF:

Radiofrequency

SC:

Subcutaneous

SST:

Spinal thalamic tract

VTA:

Ventral tegmental area

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Acknowledgements

The authors thank Dr. M Randall for his help in performing measurements of blood pressure. This project was supported by Merck and benefited from an MRC JREI grant in conjunction with AstraZeneca

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Authors and Affiliations

  1. E. Floor Medical School, School of Biomedical Sciences, Sir Peter Mansfield Centre of Magnetic Resonance, University of Nottingham, Nottingham, NG72UH, UK

    Y. B. Shah, L. Haynes, M. J. W. Prior, C. A. Marsden, P. G. Morris & V. Chapman

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  1. Y. B. Shah
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  2. L. Haynes
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  3. M. J. W. Prior
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  4. C. A. Marsden
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  5. P. G. Morris
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  6. V. Chapman
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Correspondence to V. Chapman.

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Shah, Y.B., Haynes, L., Prior, M.J.W. et al. Functional magnetic resonance imaging studies of opioid receptor-mediated modulation of noxious-evoked BOLD contrast in rats. Psychopharmacology 180, 761–773 (2005). https://doi.org/10.1007/s00213-005-2214-6

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  • DOI: https://doi.org/10.1007/s00213-005-2214-6

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