Mirtazapine antagonises the subjective, hormonal and neuronal effects of m-chlorophenylpiperazine (mCPP) infusion: A pharmacological-challenge fMRI (phMRI) study
Abstract
Aberrant signalling through central 5-HT2C receptor pathways has been implicated in various psychiatric disorders but this has not been amenable to experimental investigation in the absence of a valid in-vivo biomarker of functional 5-HT2C neurotransmission. One approach is drug-challenge pharmaco-magnetic resonance imaging (phMRI). We have previously shown that intravenous administration of the 5-HT2C agonist m-chlorophenylpiperazine (mCPP) elicits increases in blood oxygenation dependent signal (BOLD) in regions consistent with the distribution of 5-HT2C receptors. In the current study we determined whether BOLD signal responses to mCPP could be blocked by pre-treatment with a 5-HT2C antagonist. Healthy male volunteers received oral mirtazapine, 5-HT2/5-HT3 receptor antagonist, or placebo 90min prior to intravenous mCPP challenge phMRI. BOLD signal increases following mCPP infusion occurred in areas known to be rich in 5-HT2C receptors such as the substantia nigra, hypothalamus, pallidum and amygdala. These responses were attenuated by mirtazapine pre-treatment. The results suggest that mCPP-challenge phMRI produces reliable patterns of response that are mediated by 5-HT2C receptors; these responses may therefore be useful in-vivo measures of 5-HT2C function in psychiatric disorders. © 2011 Elsevier Inc.
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Date
2011
Type
Article
Subject
Brain, Hormones, Drug therapy, Magnetic resonance imaging
Citation
McKie, S., Richardson, P., Elliott, R., Vollm, B. A., Dolan, M. C., Williams, S. R., Anderson, I. M. & Deakin, J. F. W. (2011). Mirtazapine antagonises the subjective, hormonal and neuronal effects of m-chlorophenylpiperazine (mCPP) infusion: A pharmacological-challenge fMRI (phMRI) study. NeuroImage, 58 (2), pp.497-507.