Markers associated with testosterone enhancement of methamphetamine-induced striatal dopaminergic neurotoxicity.
Animals; Biomarkers/metabolism; Blotting; Body Temperature/drug effects; Body Weight/drug effects; Corpus Striatum/*drug effects/metabolism; Dopamine Plasma Membrane Transport Proteins/metabolism; Dopamine/*metabolism; Drug Synergism; HSP70 Heat-Shock Proteins/metabolism; Inbred Strains; Male; Methamphetamine/*toxicity; Mice; Neurotoxicity Syndromes/*etiology/metabolism; Oxidative Stress/drug effects; Testosterone Propionate/*pharmacology; Vesicular Monoamine Transport Proteins/metabolism; Western
Intact male CD-1 mice received an injection of testosterone propionate (TP–5 ug), progesterone (P–5 mg), the oil vehicle or remained untreated (control). At 24 hours after hormonal treatments the mice received an injection of methamphetamine (MA–40 mg/kg) and rectal temperatures were measured. At 5 days post-MA, assays were performed to assess effects of these treatments. Maximal increases in body temperatures, that were significantly greater than oil-treated controls, were obtained in TP-treated mice. At 5 days post-MA, maximal weight reductions were obtained with TP-treated mice, while P-treated mice showed no significant decrease between the pre- versus post-MA determinations. Striatal dopamine concentrations showed maximal reductions and heat-shock protein-70 maximal increases in the TP group, with both differing significantly as compared with all other groups. Protein levels of dopamine transporters were significantly decreased in P-treated mice, while vesicular monoamine transporter-2 was significantly decreased in TP-treated mice. Taken together, these results suggest that testosterone exacerbates the deleterious effects of MA within male mice as indicated by a number of markers related to neurotoxicity. The changes in markers as associated with this enhanced neurotoxicity suggest that TP may increase thermal/energy responses and/or oxidative stress to produce this effect.
Buletko A Blake; Dluzen Dean E; McDermott Janet L; Darvesh Altaf S; Geldenhuys Werner J
Neurotoxicology and teratology
2012
2012-06
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/10.1016/j.ntt.2012.03.003" target="_blank" rel="noreferrer noopener">10.1016/j.ntt.2012.03.003</a>
Effects of a novel dopamine uptake inhibitor upon extracellular dopamine from superfused murine striatal tissue.
Animals; Biological Transport/drug effects; Buffers; Calcium Channels/metabolism; Dopamine Plasma Membrane Transport Proteins/metabolism; Dopamine Uptake Inhibitors/*pharmacology; Dopamine/*metabolism; Extracellular Space/*drug effects/*metabolism; In Vitro Techniques; Male; Methamphetamine/pharmacology; Mice; Neostriatum/*cytology/drug effects; PC12 Cells; Perfusion; Potassium Channel Blockers/pharmacology; Potassium Channels; Potassium Chloride/pharmacology; Rats; Voltage-Gated/antagonists & inhibitors
The dopamine transporter (DAT) plays an important role in substance abuse, schizophrenia, and dopaminergic toxicity associated with the Parkinsonian animal model toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Accordingly, the DAT serves as a critical component in regulating dopaminergic function in health and disease states. We have been working with a novel cage compound,
Geldenhuys Werner J; Bezuidenhout Lois-May; Dluzen Dean E
European journal of pharmacology
2009
2009-10
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/10.1016/j.ejphar.2009.08.012" target="_blank" rel="noreferrer noopener">10.1016/j.ejphar.2009.08.012</a>