Tamoxifen diminishes methamphetamine-induced striatal dopamine depletion in intact female and male mice.
Animals; Catecholamines/metabolism; Corpus Striatum/drug effects/*metabolism; Dopamine Uptake Inhibitors/*pharmacology; Dopamine/*metabolism; Estrogen Antagonists/*pharmacology; Female; Humans; Hypothalamus/metabolism; Inbred Strains; Male; Methamphetamine/*pharmacology; Mice; Neurotoxins/*pharmacology; Olfactory Bulb/metabolism; Organ Size/drug effects; Pituitary Gland/anatomy & histology; Tamoxifen/*pharmacology
It has been demonstrated that the nigrostriatal dopaminergic system of male mice is more sensitive to the neurotoxic effects of methamphetamine (MA). The basis for this difference can be related to oestrogen, which has the capacity to function as a neuroprotectant against neurotoxins that target the nigrostriatal dopaminergic system. We examined the effects of the anti-oestrogen, tamoxifen (TMX), upon MA-induced neurotoxicity of the nigrostriatal dopaminergic system in intact female and male CD-1 mice. Striatal dopamine concentrations of TMX-treated female and male mice receiving MA were significantly greater than mice receiving MA alone. In female, but not male, mice, oestrogen treatment also resulted in greater striatal dopamine concentrations compared to mice receiving MA alone. Interestingly, male mice treated with oestrogen were particularly sensitive to the acute toxic effects of MA and displayed no evidence of nigrostriatal neuroprotection. The dihydroxyphenylacetic acid/dopamine ratios following MA for female and male mice treated with TMX or females treated with oestrogen were significantly reduced compared to MA-treated mice and oestrogen + MA-treated male mice. No differences among the treatment groups were obtained for dopamine in the hypothalamus or olfactory bulb. These data demonstrate that TMX treatment of intact female and male mice diminishes striatal dopamine depletions to the nigrostriatal dopaminergic neurotoxin, MA. Oestrogen also displayed this capacity when administered to female, but accentuated acute toxicity in male mice. These effects are relatively specific for the nigrostriatal dopaminergic system. Such data suggest that TMX can function as a nigrostriatal dopaminergic neuroprotectant against MA-induced neurotoxicity in intact female and male mice.
Dluzen D E; McDermott J L; Anderson L I
Journal of neuroendocrinology
2001
2001-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1046/j.1365-2826.2001.00675.x" target="_blank" rel="noreferrer noopener">10.1046/j.1365-2826.2001.00675.x</a>
Alteration of dopamine release by rat caudate putamen tissues superfused with alpha 2-macroglobulin.
alpha-Macroglobulins/drug effects/*pharmacology/physiology; Alzheimer Disease/metabolism; Animals; Caudate Nucleus/*drug effects/metabolism; Chemical; Dopamine/*metabolism; Male; Methylamines/pharmacology; Nerve Growth Factor/physiology; Nerve Growth Factors/physiology; Neurotoxins/*pharmacology; Parkinson Disease/metabolism; Perfusion; Putamen/*drug effects/metabolism; Rats; Receptors; Sprague-Dawley; Stimulation
Monoamine-activated alpha-2-macroglobulin (alpha 2M) has been shown to decrease the dopamine concentrations in rat caudate putamen (CP) in vivo as well as inhibit choline acetyltransferase activities in the culture of basal forebrain neurons. In this study, we further investigated the effects of methylamine-activated alpha 2M (MA-alpha 2M) upon striatal dopaminergic function by determining whether a direct infusion of this glycoprotein will alter dopamine (DA) release in vitro from superfused CP tissue fragments. In experiment 1, an infusion of 2.8 microM MA-alpha 2M produced a statistically significant increase in DA release compared with control superfusions. In experiment 2, varying doses (0, 0.7, 1.4, 2.8, 4.1 microM) of MA-alpha 2M were tested for their capacity to alter DA release. Only the 2.8 microM dose of MA-alpha 2M was effective in producing a significant increase of DA release. In experiment 3, the normal form of alpha 2M (N-alpha 2M) at 2.8 microM was compared with the control superfusions. The infusion of N-alpha 2M produced an increase in DA release which was substantially lower than the DA increase induced by MA-alpha 2M, and not significantly different from that of the control superfusion. These results show that MA-alpha 2M, like some other neurotoxins, can markedly alter CP dopaminergic function as indicated by the acute increase in DA release following infusion of this glycoprotein, and these effects are exerted at a relatively narrow range of doses. Taken together, these data suggest that this glycoprotein, if allowed to accumulate in the central nervous system (CNS), may promote some neurodegenerative changes that can occur in disorders like Parkinson's disease.
Hu Y Q; Liu B J; Dluzen D E; Koo P H
Journal of neuroscience research
1996
1996-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/jnr.490430109" target="_blank" rel="noreferrer noopener">10.1002/jnr.490430109</a>