title: 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-HT(2C) 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-HT(2C) neurotransmission. One approach is drug-challenge pharmaco-magnetic resonance imaging (phMRI). We have previously shown that intravenous administration of the 5-HT(2C) agonist m-chlorophenylpiperazine (mCPP) elicits increases in blood oxygenation dependent signal (BOLD) in regions consistent with the distribution of 5-HT(2C) receptors. In the current study we determined whether BOLD signal responses to mCPP could be blocked by pre-treatment with a 5-HT(2C) antagonist. Healthy male volunteers received oral mirtazapine, 5-HT(2)/5-HT(3) 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-HT(2C) 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-HT(2C) receptors; these responses may therefore be useful in-vivo measures of 5-HT(2C) function in psychiatric disorders.
authors: Neuroscience & Psychiatry Unit, University of Manchester, Manchester, UK. shane.mckie@manchester.ac.uk
authors: Shane
authors: S
authors: McKie
authors: Paul
authors: P
authors: Richardson
authors: Rebecca
authors: R
authors: Elliott
authors: Birgit A
authors: BA
authors: Völlm
authors: Mairead C
authors: MC
authors: Dolan
authors: Steve R
authors: SR
authors: Williams
authors: Ian M
authors: IM
authors: Anderson
authors: J F William
authors: JF
authors: Deakin
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004311:Double-Blind Method; D006728:Hormones / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000078785:Mirtazapine; D010100:Oxygen / Q000097:blood; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology*; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D006728:Hormones; D010879:Piperazines; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D008803:Mianserin; D000078785:Mirtazapine; C015068:1-(3-chlorophenyl)piperazine; D010100:Oxygen; D006854:Hydrocortisone