5-HT(2C) receptor activation by m-chlorophenylpiperazine detected in humans with fMRI

Functional brain imaging using selective drug probes offers the opportunity to investigate regional neuronal activation linked to receptor stimulation or inhibition. In a placebo-controlled, balanced order design in eight male volunteers, the 5-HT(2c) agonist, m-chlorophenylpiperazine (mCPP) increased blood oxygen level dependent (BOLD) signal in the hypothalamus, caudate, pallidum, amygdala and pyriform cortex, anterior cingulate gyrus and choroid plexus (p < 0.001 uncorrected), areas with high density of 5-HT(2c) receptors. Activation in the hypothalamus correlated significantly with the prolactin response (p < 0.05 small volume corrected). In a subsequent Go/NoGo task, mCPP enhanced activation in right lateral orbitofrontal cortex (p < 0.05 small volume corrected). These findings suggest that pharmacoMRI is a potentially powerful tool for investigating neurotransmitter function in humans.