Role of 5-HT(2) receptor subtypes in depletion of 5-HT induced by p-chloroamphetamine in the mouse frontal cortex

A serotonin (5-hydroxytryptamine, 5-HT)-releasing drug, p-chloroamphetamine elicited decreases in 5-HT levels in the mouse frontal cortex. 5-HT reduction elicited by p-chloroamphetamine was inhibited by the 5-HT(2A/2B/2C) receptor antagonist, LY 53857 and the 5-HT(2A) receptor antagonist, ketanserin. However, the 5-HT(2B/2C) receptor antagonist, SB 206553, enhanced it. LY 53857 and ketanserin can inhibit hyperthermia elicited by p-chloroamphetamine, although SB 206553 enhances it. The effects of the 5-HT(2) receptor antagonists on neurotoxicity are very similar to those on hyperthermia. Since hyperthermia facilitates neurotoxicity induced by amphetamine analogue, these 5-HT(2) receptor antagonists may modify 5-HT depletion induced by p-chloroamphetamine through responses to body temperature.