Pre- and postsynaptic neurochemical alterations following estrogen-induced striatal dopamine hypo- and hypersensitivity.
The administration of pharmacologic doses of estrogen results in a biphasic response in striatal dopamine sensitivity, as measured by apomorphine-induced stereotypy. At 24 hr after the last dose of estradiol benzoate (EB) there is a suppression of apomorphine-induced stereotypy, which is followed by an increased sensitivity to apomorphine at 48 hr. The dopamine hyposensitivity is reflected postsynaptically by an increased KD (i.e., decreased affinity) for 3H-spiroperidol binding to striatal membranes, while the hypersensitive phase is reflected by an increased Bmax for 3H-spiroperidol binding to striatal membranes. Presynaptically during the hyposensitive phase the tyrosine hydroxylase displayed a decreased KM for the pterine cofactor. The decreased KM for the cofactor was retained in the hypersensitive animals, however the Vmax for tyrosine hydroxylase was decreased during the hypersensitive phase of the EB-induced changes in dopamine sensitivity. The presynaptic or autoreceptor sensitivity of the dopamine neurons projecting to the striatum was assessed by determining the apomorphine IC50 value for the inhibition of synaptosomal tyrosine hydroxylase activity. Utilizing this assay the animals that were hyposensitive to dopamine showed a normal presynaptic sensitivity, while those animals that had developed a hypersensitivity to dopamine following EB were also hypersensitive to dopamine presynaptically.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001923:Brain Chemistry; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D004298:Dopamine / Q000009:adverse effects*; D004342:Drug Hypersensitivity / Q000209:etiology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D004967:Estrogens; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D004298:Dopamine