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

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 90 min 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. --------------------------------------------------------------------------------