Effects of tamoxifen on striatal dopamine and 5-hydroxytryptamine release in freely moving male rats: an in-vivo microdialysis investigation.
Recent studies indicating interaction of oestrogens with central cholinergic, dopaminergic and 5-HTergic systems have led to the assumption of a protective role of oestrogens in certain neurodegenerative disorders. The non-steroidal drug tamoxifen, a mixed oestrogen agonist-antagonist, has been shown to modulate central nervous system functions in the corpus striatum. In this study we used a microdialysis technique to examine the effects of tamoxifen upon the striatal dopaminergic and 5-HTergic systems in intact freely moving male rats. The extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid were measured after intraperitoneal administration of either the control or tamoxifen, and were compared with their corresponding baseline levels. Significant 25-35% increases in the baseline levels of dopamine and 3,4-dihydroxyphenylacetic acid were observed after the highest doses of tamoxifen (1.5 mg kg(-1) and 30 mg kg(-1), respectively), whereas the lowest dose of tamoxifen (0.3 mg kg(-1)) elevated dopamine and 3,4-dihydroxyphenylacetic acid levels by a detectable 15% of the basal. In addition, the ratio of 3,4-dihydroxyphenylacetic acid-to-dopamine remained unchanged in comparison with that of the pretreatment levels. Whereas no change in the striatal 5-hydroxyindoleacetic acid concentrations was seen with the lowest and highest dose regimen, the intermediate dose elicited a moderate increase (20%) in basal 5-hydroxyindoleacetic acid levels. The pharmacological relevance of the effects of tamoxifen on the dopaminergic and 5-HTergic systems, as a prelude to the development of non-steroidal oestrogenic compounds in reducing the risk of neurodegenerative disorders such as Alzheimer's disease, is discussed.
College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, NY 11439, USA.
C S
CS
Chaurasia
C E
CE
Chen
J
J
Rubin
S L
SL
Dewey
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology*
D004965:Estrogen Antagonists; D013629:Tamoxifen; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid