Cs. Chaurasia et al., Effects of tamoxifen on striatal dopamine and 5-hydroxytryptamine release in freely moving male rats: An in-vivo microdialysis investigation, J PHARM PHA, 50(12), 1998, pp. 1377-1385
Recent studies indicating interaction of oestrogens with central cholinergi
c, dopaminergic and 5-HTergic systems have led to the assumption of a prote
ctive role of oestrogens in certain neurodegenerative disorders. The non-st
eroidal drug tamoxifen, a mixed oestrogen agonist-antagonist, has been show
n to modulate central nervous system functions in the corpus striatum. In t
his study we used a microdialysis technique to examine the effects of tamox
ifen upon the striatal dopaminergic and 5-HTergic systems in intact freely
moving male rats.
The extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid, homov
anillic acid and 5-hydroxyindoleacetic acid were measured after intraperito
neal administration of either the control or tamoxifen, and were compared w
ith their corresponding baseline levels. Significant 25-35% increases in th
e baseline levels of dopamine and 3,4-dihydroxyphenylacetic acid were obser
ved after the highest doses of tamoxifen (1.5 mg kg(-1) and 3.0 mg kg(-1) r
espectively), 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-dopa
mine remained unchanged in comparison with that of the pretreatment levels.
Whereas no change in the striatal 5-hydroxyindoleacetic acid concentration
s was seen with the lowest and highest dose regimen, the intermediate dose
elicited a moderate increase (20%) in basal 5-hydroxyindoleacetic acid leve
ls.
The pharmacological relevance of the effects of tamoxifen on the dopaminerg
ic and 5-HTergic systems, as a prelude to the development of non-steroidal
oestrogenic compounds in reducing the risk of neurodegenerative disorders s
uch as Alzheimer's disease, is discussed.