Effect of mCPP on Cognitive Control, Appetite, and Neural Responses

Previous studies have reported that the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) decreases appetite and food intake in humans1-3. 5-HT2C receptor activation inhibits dopamine and norepinephrine release in the brain4, and has also been linked to diabetes5. The specificity of the effect of mCPP on human appetite is unclear, as previous studies also reported an increase in nausea1,3. The drug has also been reported to increase anxiety and cause panic attacks when given in a bolus dose intravenously6. Previous findings in our laboratory showed that mCPP reduced appetite, increased satiety in women and enhanced memory in the P1vital® Oxford Emotional Test Battery3. Following up on these results a food intake and fMRI study was performed, in which it was observed that mCPP decreased intake of a palatable snack (hedonic eating) and dlPFC and insula BOLD responses to food pictures. Additionally it increased memory and food value responses in brain after mCPP administration (Thomas et al submitted). It is well established that eating behaviour is affected by metabolic signals (e.g. insulin, ghrelin, serotonin) and is also modulated via food reward processes7. More recently it has been proposed that eating is also modulated via higher cognitive processes such as inhibitory control, attention, and memory. However, in humans, eating behaviour seems to be a more complex process, which involves habits, long-term goals and social interaction. Thus, cognitive processes appear to play an important role in food consumption. In the proposed study the researchers investigate the effect of administering mCPP, on eating, and on metabolic, reward and cognitive processes and the potential interplay between these functions.