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Guanfacine produces differential effects in frontal cortex compared with striatum: assessed by phMRI BOLD contrast

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Abstract

Rationale

Guanfacine (an alpha-2A adrenoreceptor agonist) is a drug of benefit in the treatment of attention deficit hyperactivity disorder (ADHD) (Taylor FB, Russo J, J Clin Psychopharmacol 21:223–228, 2001). Assessment of this drug using neuroimaging will provide information about the brain regions involved in its effects.

Objectives

The pharmacological magnetic resonance imaging blood oxygenation level dependent (BOLD) response was determined in rat brain regions following administration of guanfacine.

Methods

Male rats were individually placed into a 2.35 T Bruker magnet for 60 min to achieve basal recording of changes in signal intensity. Either saline (n = 9) or guanfacine (0.3 mg/kg, i.p.; n = 9) was then administered and recording was continued for a further 90 min. Data were analysed for BOLD effects using statistical parametric maps. Respiration rate, blood pressure and blood gases were monitored and remained constant throughout scanning.

Results

The main changes observed were negative BOLD effects in the caudate putamen and nucleus accumbens with positive BOLD effects in frontal association, prelimbic and motor cortex areas.

Conclusions

These data suggest that guanfacine can decrease neuronal activity in the caudate while increasing frontal cortex activity. This ability to change neuronal activity in specific areas of rat brain that are known to be impaired in ADHD (Solanto MV, Behav Brain Res 130:65–71, 2002) may contribute to guanfacine’s beneficial effects.

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Acknowledgement

This work was funded by Shire Pharmaceuticals.

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Authors and Affiliations

  1. School of Biomedical Sciences, Medical School, Institute of Neuroscience, University of Nottingham, Queens Medical Centre, Nottingham, NG7 2UH, UK

    Neil Easton, Kevin C. Fone & Charles A. Marsden

  2. Institute of Neuroscience, Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, University Park, Nottingham, UK

    Yasmene B. Shah

  3. Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB1 2QJ, UK

    Fiona H. Marshall

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  1. Neil Easton
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  2. Yasmene B. Shah
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  3. Fiona H. Marshall
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  4. Kevin C. Fone
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  5. Charles A. Marsden
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Correspondence to Neil Easton.

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Easton, N., Shah, Y.B., Marshall, F.H. et al. Guanfacine produces differential effects in frontal cortex compared with striatum: assessed by phMRI BOLD contrast. Psychopharmacology 189, 369–385 (2006). https://doi.org/10.1007/s00213-006-0558-1

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