oxalates and Fever

Methamphetamine (METH) causes hyperthermia and dopaminergic neurotoxicity in the rodent striatum. METH interacts with σ receptors and σ receptor antagonists normally mitigate METH-induced hyperthermia and dopaminergic neurotoxicity. The present study was undertaken because in two experiments, pretreatment with σ receptor antagonists failed to attenuate METH-induced hyperthermia in mice. This allowed us to determine whether the ability of σ receptor antagonists (AZ66 and AC927) to mitigate METH-induced neurotoxicity depends upon their ability to modulate METH-induced hyperthermia.. Mice were treated using a repeated dosing paradigm and body temperatures recorded. Striatal dopamine was measured one week post-treatment.. The data indicate that the ability of σ receptor antagonists to attenuate METH-induced dopaminergic neurotoxicity is linked to their ability to block METH-induced hyperthermia.. The ability of σ receptor antagonists to mitigate METH-induced hyperthermia may contribute to its neuroprotective actions.

Topics: Animals; Benzothiazoles; Body Temperature; Corpus Striatum; Dopamine; Dopamine Agents; Fever; Male; Methamphetamine; Mice; Neurotoxicity Syndromes; Oxalates; Piperazines; Piperidines; Receptors, sigma

Methamphetamine interacts with sigma (σ) receptors and AC927, a selective σ receptor ligand, protects against methamphetamine-induced dopaminergic neurotoxicity. In the present study, the effects of AC927 on methamphetamine-induced hyperthermia and striatal serotonergic neurotoxicity were evaluated. Male, Swiss Webster mice were injected (i.p.) every 2 h, for a total of four times, with one of the following treatments: Saline+Saline; Saline+Methamphetamine (5 mg/kg); AC927 (5, 10, 20 mg/kg)+Methamphetamine (5 mg/kg); or AC927 (5, 10, 20 mg/kg)+Saline. Pretreatment with AC927 (10 mg/kg) significantly attenuated methamphetamine-induced striatal serotonin depletions, striatal serotonin transporter reductions, and hyperthermia. At the doses tested, AC927 itself had no significant effects on serotonin levels, serotonin transporter expression, or body temperature. To evaluate the effects of higher ambient temperature on methamphetamine-induced neurotoxicity, groups of mice were treated at 37 °C. Overall, there was an inverse correlation between the body temperature of the animals and striatal serotonin levels. Together, the data suggest that AC927 (10 mg/kg) protects against methamphetamine-induced neurotoxicity. The reduction of methamphetamine-induced hyperthermia by AC927 may contribute to the observed neuroprotection in vivo.

Topics: Animals; Body Temperature; Fever; Ligands; Male; Methamphetamine; Mice; Neuroprotective Agents; Oxalates; Piperidines; Receptors, sigma; Serotonin; Serotonin Plasma Membrane Transport Proteins; Visual Cortex

Topics: Abdomen; Child; Child, Preschool; Diet; Diet Therapy; Female; Fever; Humans; Male; Migraine Disorders; Nausea; Oxalates; Pain Management; Photosensitivity Disorders; Syndrome; Vomiting