Possible link between brain serotonin metabolism and methionine sulfoximine-induced hypothermia and associated behavior in the rat.
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.
Ginefri-Gayet
M
M
Laboratoire de Physiologie Générale, Faculté des Sciences, Université de Nancy, Vandoeuvre-lès-Nancy, France.
Gayet
J
J
D006916:5-Hydroxytryptophan / Q000097:blood; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D010134:Fenclonine / Q000494:pharmacology; D005277:Fenfluramine / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D008717:Methionine Sulfoximine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D010133:p-Chloroamphetamine / Q000494:pharmacology
D005230:Fatty Acids, Nonesterified; D008717:Methionine Sulfoximine; D005277:Fenfluramine; D012701:Serotonin; D010133:p-Chloroamphetamine; D006916:5-Hydroxytryptophan; D010134:Fenclonine