Serotonin receptors in the caudal brainstem are necessary and sufficient for the anorectic effect of peripherally administered mCPP

Abstract

 The role of caudal brainstem 5-HT receptors in mediating the anorectic effect of the direct 5-HT_2C/1B agonist, mCPP [1-(3-chlorophenyl)piperazine dihydrochloride], was evaluated. We demonstrated, first, that systemic injections of mCPP yielded a dose-related suppression of intra-oral intake of 12.5% glucose in intact rats and in chronically maintained supracollicular decerebrate rats. The results of the decerebrate experiment suggest that 5-HT receptors in the caudal brainstem are sufficient for mediating the drug’s intake effect. We also showed a dose-related intake suppression when mCPP was delivered to the fourth ventricle of intact rats, with potent suppression obtained at doses well below threshold for systemic administration. Whether and to what extent the 5-HT_2C/2A antagonist, mesulergine reverses the intake suppression that follows systemic or 4th ICV injection of mCPP was examined. Fourth ICV co-administration of mesulergine (60 μg) and mCPP (40 μg) eliminated the approximately 50% intake suppression observed when mCPP was delivered alone, a result that affirms the receptor selectivity of the 4th ICV agonist effect. We showed, further, that 4th ICV mesulergine (60 μg) completely reversed the intake suppression produced by systemic mCPP (2 mg/kg). The latter result indicates that stimulation of 5-HT receptors in the caudal brainstem is necessary for the intake suppression produced by systemic administration of this 5-HT agonist in the intact rat.