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Functional magnetic resonance imaging and c‐Fos mapping in rats following a glucoprivic dose of 2‐deoxy‐d‐glucose
Author(s) -
Dodd Garron T.,
Williams Steve R.,
Luckman Simon M.
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06671.x
Subject(s) - orbitofrontal cortex , nucleus accumbens , neuroscience , brainstem , functional magnetic resonance imaging , striatum , hypothalamus , ventral pallidum , ventral tegmental area , psychology , endocrinology , medicine , central nervous system , prefrontal cortex , basal ganglia , globus pallidus , dopamine , cognition , dopaminergic
J. Neurochem. (2010) 113 , 1123–1132. Abstract The glucose analogue, 2‐deoxy‐ d ‐glucose (2‐DG) is an inhibitor of glycolysis and, when administered systemically or centrally, induces glucoprivation leading to counter‐regulatory responses, including increased feeding behaviour. Investigations into how the brain responds to glucoprivation could have important therapeutic potential, as disruptions or defects in the defence of the brain’s ‘glucostatic’ circuitry may be partly responsible for pathological conditions resulting from diabetes and obesity. To define the ‘glucostat’ brain circuitry further we have combined blood‐oxygen‐level‐dependent pharmacological‐challenge magnetic resonance imaging (phMRI) with whole‐brain c‐Fos functional activity mapping to characterise brain regions responsive to an orexigenic dose of 2‐DG [200 mg/kg; subcutaneous (s.c.)]. For phMRI, rats were imaged using a T 2 *‐weighted gradient echo in a 7T magnet for 60 min under α‐chloralose anaesthesia, whereas animals for immunohistochemistry were unanaesthetised and freely behaving. These complementary methods demonstrated functional brain activity in a number of previously characterised glucose‐sensing brain regions such as those in the hypothalamus and brainstem following administration of 2‐DG compared with vehicle. As the study mapped whole‐brain functional responses, it also identified the orbitofrontal cortex and striatum (nucleus accumbens and ventral pallidum) as novel 2‐DG‐responsive brain regions. These regions make up a corticostriatal connection with the hypothalamus, by which aspects of motivation, salience and reward can impinge on the hypothalamic control of feeding behaviour. This study, therefore, provides further evidence for a common integrated circuit involved in the induction of feeding behaviour, and illustrates the valuable potential of phMRI in investigating central pharmacological actions.