Effects of the 5-HT2C/2B receptor agonist 1-(3-chlorophenyl)piperazine on plasma glucose levels of rats

Acute administration of the 5-HT2C/2B receptor agonist 1-(3-chlorophenyl)piperazine (mCPP, 5-10 mg/kg i.p.) induced hyperglycemia in rats. These changes were diminished in a dose-dependent manner by the 5-HT1/5-HT2 receptor antagonist methysergide and the 5-HT2A/2B/2C receptor antagonist ritanserin. In addition, mCPP-induced hyperglycemia was dose dependently diminished by the ganglionic blocker hexamethonim and was prevented by prior adrenodemedullation. Neither the 5-HT2A receptor antagonist ketanserin nor the 5-HT3/5-HT4 receptor antagonist (3-alpha-tropanyl)-1H-indole-3-carboxylic acid ester (ICS 205-930) proved effective against mCPP-induced hyperglycemia. Lastly, administration of the 5-HT2A/2C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane (DOI) increased plasma glucose levels through ketanserin- and ritanserin-sensitive processes. Our results suggest that hyperglycemia elicited by mCPP is mediated by 5-HT2C and/or (2B) receptors, and in turn adrenomedullary catecholamien release, whereas that elicited by DOI involves 5-HT2A receptors.