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Differential effects of the d- and l- isomers of amphetamine on pharmacological MRI BOLD contrast in the rat

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Abstract

Rationale

The d- and l-amphetamine sulphate isomers are used in the formulation of Adderall XR®, which is effective in the treatment of attention-deficit hyperactivity disorder (ADHD). The effects of these isomers on brain activity has not been examined using neuroimaging.

Objectives

This study determines the pharmacological magnetic resonance imaging blood-oxygenation-level-dependent (BOLD) response in rat brain regions after administration of each isomer.

Materials and methods

Rats were individually placed into a 2.35 T Bruker magnet for 60 min to achieve basal recording of variation in signal intensity. Either saline (n = 9), d-amphetamine sulphate (2 mg/kg, i.p.; n = 9) or l-amphetamine sulphate (4 mg/kg, i.p.; n = 9) were administered, and recording continued for a further 90 min. Data were analysed for BOLD effects using statistical parametric maps. Blood pressure, blood gases and respiratory rate were monitored during scanning.

Results

The isomers show overlapping effects on the BOLD responses in areas including nucleus accumbens, medial entorhinal cortex, colliculi, field CA1 of hippocampus and thalamic nuclei. The l-isomer produced greater global changes in the positive BOLD response than the d-isomer, including the somatosensory and motor cortices and frontal brain regions such as the orbitofrontal cortices, prelimbic and infralimbic cortex which were not observed with the d-isomer.

Conclusions

The amphetamine isomers produce different BOLD responses in brain areas related to cognition, pleasure, pain processing and motor control probably because of variations on brain amine systems such as dopamine and noradrenaline. The isomers may, therefore, have distinct actions on brain regions affected in ADHD patients.

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Acknowledgements

The authors wish to thank Malcolm Prior for MRI technical assistance. This work was funded by Shire pharmaceuticals.

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

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

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

    Fiona Marshall

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Correspondence to Kevin C. F. Fone.

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Easton, N., Marshall, F., Fone, K.C.F. et al. Differential effects of the d- and l- isomers of amphetamine on pharmacological MRI BOLD contrast in the rat. Psychopharmacology 193, 11–30 (2007). https://doi.org/10.1007/s00213-007-0756-5

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