Possible link between brain serotonin metabolism and methionine sulfoximine-induced hypothermia and associated...

L-Methionine-D,L-sulfoximine (MSO) intraperitoneally or intracerebroventricularly (third ventricle) injected at convulsant doses induced a hypothermia, primarily associated with a syndrome of ataxia, in the restrained rat maintained at an ambient temperature of 23 degrees C. Depletion of brain serotonin (5-HT) by pretreatment with p-chlorophenylalanine (PCPA), p-chloroamphetamine (PCA), and d-fenfluramine (FFA) did not significantly modify the time course and magnitude of MSO-induced developing hypothermia but it enhanced abnormal motor behavior. Enhancement of 5-HT synthesis in MSO-submitted rats pretreated with 5-hydroxytryptophan (5-HTP) (200 mg/kg, IP) alone or 5-HTP (100 mg/kg, IP) preassociated with carbidopa (10 mg/kg, IP) suppressed significantly hypothermia, but it did not greatly modify motor disturbances. In conclusion, the neurocytochemical processes initiating hypothermia following administration of MSO to the rat appear to be linked to a slowdown of the rate of brain 5-HT turnover, maybe at the level of the midbrain raphe nuclei.