Involvement of striatum serotonergic system in the expression of genetically defined catalepsy.
The activity of the rate-limiting enzyme of serotonin biosynthesis, tryptophan hydroxylase, and specific binding of [3H]ketanserin to 5-HT2A receptors and [3H]8-OH-DPAT to 5-HT1A receptors in the striatum of genetically predisposed to catalepsy rats and mice have been studied. The activity of tryptophan hydroxylase in the striatum of rats bred for many generations for predisposition to catalepsy was higher than in nonselected rats. Mice of highly susceptible to pinch-induced catalepsy CBA strain also differed from noncataleptic AKR and C57BL mouse strains by higher activity of tryptophan hydroxylase in striatum. Inhibition of tryptophan hydroxylase with p-chlorophenylalanine or p-chloromethamphetamine significantly decreased immobility time in genetically predisposed to catalepsy rats and mice. A decrease in the [3H]ketanserin specific binding in the striatum of cataleptic rats and CBA mice was found indicating a decrease in 5-HT2A receptor density. A decrease in [3H]8-OH-DPAT binding in striatum of cataleptic rats but not in CBA mice was shown. These results indicate that serotonergic system of striatum is involved in the expression of hereditary catalepsy and suggest that hereditary catalepsy may result from genetic changes in the regulation of serotonin metabolism and reception in striatum.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D002375:Catalepsy / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D003342:Corpus Striatum / Q000201:enzymology / Q000378:metabolism*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000096:biosynthesis*; D013045:Species Specificity; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; D014365:Tryptophan Hydroxylase