Activation of 5-HT2 receptors induces glycogenolysis in the rat brain.

The effect of 5-HT(2) receptor activation on brain glycogen and the extracellular concentration of glucose was investigated in the present study. An injection of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (2 mg/kg, i.p.) or mescaline (10 mg/kg, i.p.) at an ambient temperature of 29 degrees C produced a 35-45% decrease in brain glycogen that persisted for at least 2 h. DOI also increased the extracellular concentration of glucose in the striatum by 60%. Maintenance of rats at 22 degrees C significantly attenuated DOI-induced glycogenolysis, as well as DOI-induced hyperthermia, and the increase in the extracellular concentration of glucose in the striatum. DOI-induced hyperthermia, glycogenolysis and increase in the extracellular concentration of glucose also were attenuated in rats treated with the 5-HT(2) receptor antagonist, 6-methyl-1-(methylethyl)-ergoline-8beta-carboxylic acid 2-hydroxy-1-methylpropyl ester maleate (LY-53,857) (3 mg/kg, ip). These results support the conclusion that 5-HT(2) receptor activation promotes glycogenolysis and that hyperthermia exerts a prominent role in this process.