5-HT2C receptor activation inhibits appetitive and consummatory components of feeding and increases brain c-fos immunoreactivity in mice

5-Hydroxytryptamine (5-HT)2C and 5-HT1B receptors are implicated in the inhibitory modulation of feeding behaviour. However, their respective, and possibly different, roles have not been clearly identified because of a lack of selective 5-HT2C receptor agonists. Here, using the putative, selective 5-HT2C receptor agonist VER23779, we show that its effects on feeding are fully reversed by pretreatment with a selective 5-HT2C receptor antagonist, but unaffected by pretreatment with either a 5-HT1B or a 5-HT2A receptor antagonist. In mice eating a palatable mash, feeding ends earlier, inactivity is increased but the behavioural satiety sequence is preserved. In a second-order schedule of reinforcement with an initial, non-food-reinforced appetitive phase, VER23779 produces a much greater relative reduction in appetitive responding than the 5-HT1B receptor agonist CP-94,253. Increased c-fos immunoreactivity patterns following VER23779 also differ from those described for CP-94,253, in particular showing strong activation of the basolateral amygdala. The different behavioural consequences of 5-HT2C and 5-HT1B receptor activation may relate to the patterns of c-fos immunoreactivity. In particular, the basolateral amygdala may have a role in maintaining response in the appetitive phase of the second-order schedule and also be susceptible to serotonergic modulation through activation of 5-HT2C receptors.