Markers associated with testosterone enhancement of methamphetamine-induced striatal dopaminergic neurotoxicity.

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.

Nomifensine alters sex differences in striatal dopaminergic function.

A series of three experiments are presented in which the acute effects of the catecholamine reuptake inhibitor, nomifensine, upon striatal dopaminergic function are compared in female and male mice. In Experiment 1, treatment with nomifensine (5 mg kg⁻¹), at 30 min prior to injection of methamphetamine (40 mg kg⁻¹) significantly decreased the amount of striatal dopamine depletion in male, but not female, mice, thereby abolishing the sex difference in methamphetamine-induced neurotoxicity (males > females). In Experiment 2, the methamphetamine-evoked sex differences in dopamine and DOPAC output from superfused striatal tissue (males > females) were abolished in mice treated with nomifensine at 30 min prior to tissue removal.

Age-related changes in nigrostriatal dopaminergic function in heterozygous mutant dopamine transporter knock-out mice.

In this report we compared three different parameters of nigrostriatal dopaminergic (NSDA) function - locomotor activity, striatal dopamine (DA) levels and 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratios between heterozygous mutant dopamine transporter mice (+/- DAT) and their wild type controls (+/+ DAT) at three different age range periods: 4-10, 11-17 and 18-24 months of age. Locomotor activity of the +/- DAT mice failed to differ over the three age periods sampled. In +/+ DAT mice a significant decrease in locomotor activity was obtained at the 18-24-month old period compared with scores at the two earlier age periods.

Estrogen, testosterone, and methamphetamine toxicity.

The gonadal steroid hormone, estrogen, can diminish the degree of striatal dopamine depletion resulting from methamphetamine. In this article, we describe the conditions of this estrogen neuroprotection as well as the potential for estrogen and testosterone to enhance methamphetamine-induced neurodegeneration of the nigrostriatal dopaminergic system. When administered prior to a neurotoxic regimen of methamphetamine, estrogen significantly decreases the amount of striatal dopamine depletion in intact or gonadectomized female, but not male, mice.

Developmental and genetic influences upon gender differences in methamphetamine-induced nigrostriatal dopaminergic neurotoxicity.

The gonadal steroid hormone estrogen (E) may play an important role in sex differences in methamphetamine (MA)-induced neurotoxicity of the nigrostriatal dopaminergic (NSDA) system because E can serve as a neuroprotectant in female, but not male, mice. Gonadal steroid hormones also exert important organizational/developmental effects upon the brain at critical developmental periods. In Part 1 we assessed whether organizational (neonatal) or developmental (prepubertal) effects of gonadal steroids would alter gender/E-dependent neuroprotection of MA-induced NSDA neurotoxicity.

Estrogen, anti-estrogen, and gender: differences in methamphetamine neurotoxicity.

In Part 1 of this report, we review data on the effects of estrogen (E), the anti-E tamoxifen (TMX), and testosterone (T) on methamphetamine (METH)-induced neurotoxicity in female and male CD-1 mice. Treatment of gonadectomized females with a physiological regimen of E significantly diminished the amount of striatal dopamine (DA) depletion to METH compared with non-E-treated mice. If these E-treated mice received coadministered TMX, the neuroprotective effects of E were abolished.

Striatal dopamine output is compromised within +/- BDNF mice.

We reported previously that mice lacking one brain-derived neurotrophic factor (BDNF) allele demonstrate elevated striatal dopamine (DA) concentrations but impaired behavioral responses involving the nigrostriatal dopaminergic (NSDA) system. To test the hypothesis that these elevated striatal DA concentrations are associated with perturbed NSDA functioning, we compared striatal DA output between heterozygous mutant (+/-) and wild-type littermate control (+/+) BDNF mice under conditions of an intact NSDA system, as well as following methamphetamine (MA)-induced neurotoxicity. Basal DA output from superfused CS tissue fragments did not differ between +/+ and +/- BDNF mice.