Evidence that increased 5-HT release evokes region-specific effects on blood-oxygenation level-dependent functional magnetic resonance imaging responses in the rat brain.

Preece, M; Taylor, M; Raley, J; Blamire, A; Sharp, T; Sibson, N

Journal article

Evidence that increased 5-HT release evokes region-specific effects on blood-oxygenation level-dependent functional magnetic resonance imaging responses in the rat brain.

Abstract:: This study aimed to determine the potential of in vivo functional magnetic resonance imaging (fMRI) methods as a non-invasive means of detecting effects of increased 5-HT release in brain. Changes in blood-oxygenation level-dependent (BOLD) contrast induced by administration of the 5-HT-releasing agent, fenfluramine, were measured in selected brain regions of halothane-anesthetized rats. Initial immunohistochemical measurements of the marker of neural activation, Fos, confirmed that in halothane-anesthetized rats fenfluramine (10 mg/kg i.v.) evoked cellular responses in cortical regions which were attenuated by pre-treatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (300 mg/kg i.p. once daily for 2 days). Fenfluramine-induced Fos was demonstrated in numerous glutamatergic pyramidal neurons (Fos/excitatory amino acid carrier 1 (EAAC1) co-labeled), but also a small number of GABA interneurons (Fos/glutamic acid decarboxylase (GAD)(67) colabeled). Fenfluramine (10 mg/kg i.v.) evoked changes in BOLD signal intensity in a number of cortical and sub-cortical regions with the greatest effects being observed in the nucleus accumbens (-13.0%+/-2.7%), prefrontal cortex (-10.1%+/-3.2%) and motor cortex (+2.3%+/-1.0%). Pre-treatment with p-chlorophenylalanine, significantly attenuated the response to fenfluramine (10 mg/kg i.v.) in all regions with the exception of the motor cortex which showed a trend. These experiments demonstrate that increased 5-HT release evokes region-specific changes in the BOLD signal in rats, and that this effect is attenuated in almost all regions by 5-HT depletion. These findings support the use of fMRI imaging methods as a non-invasive tool to study 5-HT function in animal models, with the potential for extension to clinical studies.

Publication status:: Published

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APA Style

Preece, M., Taylor, M., Raley, J., Blamire, A., Sharp, T., & Sibson, N. (2009). Evidence that increased 5-HT release evokes region-specific effects on blood-oxygenation level-dependent functional magnetic resonance imaging responses in the rat brain. Neuroscience, 159(2), 751–759.

MLA Style

Preece, M., et al. “Evidence That Increased 5-HT Release Evokes Region-Specific Effects on Blood-Oxygenation Level-Dependent Functional Magnetic Resonance Imaging Responses in the Rat Brain.” Neuroscience, vol. 159, no. 2, 2009, pp. 751–59.

Chicago Style

Preece, M, M Taylor, J Raley, A Blamire, T Sharp, and N Sibson. 2009. “Evidence That Increased 5-HT Release Evokes Region-Specific Effects on Blood-Oxygenation Level-Dependent Functional Magnetic Resonance Imaging Responses in the Rat Brain.” Neuroscience 159 (2): 751–59.
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