Mirtazapine antagonises the subjective, hormonal and neuronal effects of m-chlorophenylpiperazine (mCPP) infusion: A pharmacological-challenge fMRI (phMRI) study

作者：McKie Shane^*; Richardson Paul; Elliott Rebecca; Voellm Birgit A; Dolan Mairead C; Williams Steve R; Anderson Ian M; Deakin J F William

来源：NeuroImage, 2011, 58(2): 497-507.

DOI：10.1016/j.neuroimage.2011.06.049

• m-Chlorophenylpiperazine (mCPP)
• 5-HT(2c)
• Pharmacological-challenge fMRI (phMRI)
• Mirtazapine
• Cortisol
• Subjective effects

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 90 min 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.

• 出版日期2011-9-15