AbstractThe activity of the rate‐limiting enzyme of serotonin biosynthesis, tryptophan hydroxylase, in the striatum but not in the hippocampus and midbrain of rats bred for predisposition to catalepsy was higher than in nonselected rats. Mice of the highly susceptible to catalepsy CBA strain also differed from other noncataleptic mouse strains by the highest tryptophan hydroxylase activity in the striatum. Inhibition of tryptophan hydroxylase with p‐chlorophenylalanine and p‐chloromethamphetamine drastically decreased immobility time in hereditary predisposed to catalepsy animals. A decrease in the 3H‐ketanserin specific binding in the striatum of cataleptic rats and CBA mice was found. It was suggested that this decrease in 5‐HT2A serotonin receptor density represented a down regulation of the receptors due to an activation of serotonergic transmission in striatum. It is suggested that hereditary catalepsy may be resulted from genetic changes in the regulation of serotonin metabolism in striatum. © 1995 Wiley‐Liss, Inc.