Effects of long-term hormone treatment and of tibolone on monoamines and monoamine metabolites in the brains of ovariectomised, Cynomologous monkeys.
The effects of long-term hormone treatment on monoamines and monoamine metabolites in different regions of the primate brain were examined and compared. Ovariectomised Cynomologous monkeys received daily oral administration of either conjugated equine oestrogens (CEE), CEE + medroxyprogesterone acetate (MPA), or a low or high dose of tibolone, for a period of 2 years. Tissue punches collected from frozen sections through various regions of the forebrain, midbrain, and hindbrain were assayed for levels of dopamine, dihydroxyphenylacetic acid (DOPAC), serotonin, 5-hydroxyindole acetic acid (5-HIAA), and norepinephrine by high-performance liquid chromatography. Few differences between hormone-treated animals and ovariectomised controls were observed. No statistically significant effects of CEE relative to controls were detected in any of the seven brain regions analysed. Animals treated with CEE + MPA showed significant reductions in 5-HIAA in the dorsal raphe nucleus, a significant reduction in dopamine in the hypothalamus, and a significant reduction in serotonin (5-HT) levels in area 8AD of the frontal cortex. Similar to CEE, no significant effects of tibolone relative to controls were detected; however, animals treated with high-dose tibolone showed a decrease in 5-HT levels in the frontal cortex that approached significance and was similar to the effect of CEE + MPA. Collectively, the findings suggest that long-term oral administration of these compounds has relatively few effects on the levels of dopamine, serotonin, and their primary metabolites in the primate brain. This differs from the significant effects on serotonergic and dopaminergic systems detected following parenteral treatment with oestradiol and progesterone, and likely reflects differences between the effects of treating with CEE + MPA versus oestradiol and progesterone on brain monoaminergic systems.
Gibbs
R B
RB
Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, PA 15261, USA. gibbsr@pitt.edu
Edwards
D
D
Lazar
N
N
Nelson
D
D
Talameh
J
J
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004334:Drug Administration Schedule; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005260:Female; D020249:Hormone Replacement Therapy; D006728:Hormones / Q000008:administration & dosage; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008252:Macaca fascicularis; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage*; D008593:Menopause / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D009652:Norpregnenes / Q000008:administration & dosage*; D010052:Ovariectomy; D012701:Serotonin / Q000378:metabolism
D015306:Biogenic Monoamines; D020847:Estrogen Receptor Modulators; D004966:Estrogens, Conjugated (USP); D006728:Hormones; D009652:Norpregnenes; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D017258:Medroxyprogesterone Acetate; C027385:tibolone; D004298:Dopamine; D009638:Norepinephrine