Sigma (σ) receptor antagonist, BD1063, protects against methamphetamine‐induced hyperthermia and neurotoxicity in mice

Abstract

Methamphetamine (METH) is an addictive drug known to produce hyperthermia and neuronal damage. The dopaminergic pathway is particularly sensitive to METH. METH can act as a neurotoxin to dopaminergic neurons when administered at high doses or with repeated use. METH is also known to interact with σ receptors, which are located on dopaminergic neurons. The goal of the present study was to investigate whether the σ receptor antagonist, BD1063, protects against METH-induced hyperthermia and dopamine damage in the mouse brain. Male, Swiss Webster mice were injected (i.p.) every 2 hours for a total of 4 injections with one of the following treatments: saline + saline, saline + METH (5 mg/kg), BD1063 (10, 20, 30 mg/kg) + saline, or BD1063 (10, 20, 30 mg/kg) + METH (5 mg/kg). Core body temperature was measured one hour after each injection. One week after treatment, dopamine levels were measured from the striatum and cerebellum. METH significantly decreased striatal and cerebellar dopamine levels compared to saline controls. BD1063 (10–30 mg/kg) had no effect on its own on dopamine levels. Pretreatment with BD1063 (10–30 mg/kg) significantly attenuated dopamine loss induced by METH (5 mg/kg) in those brain regions studied. The neuroprotection with BD1063 was accompanied by a decrease in METH-induced hyperthermia. These results suggest that the σ receptor antagonist BD1063 protects against METH-induced hyperthermia and dopamine damage in the mouse brain. Additional studies are needed to further define the mechanisms that mediate this protective effect.