Effects of Estrogen and Progesterone on Behavioral Impairment and Neuronal Death in Ovariectomized Rats Induced by Methamphetamine

Background and purpose: Methamphetamine (METH) is one of the most powerful drugs that leads to many cognitive and behavioral side effects such as anxiety. On the other hand, studies have shown that ovarian hormones such as estrogen and progesterone have neuroprotective effects on a wide range of cognitive and behavioral disorders. The aim of this study was to investigate the role of estrogen and progesterone on anxiety-like behaviors, body temperature, brain edema, and neuronal death induced by neurotoxic regimen of methamphetamine. Materials and methods: This study was performed in 48 ovariectomized rats divided into six groups including: control, METH (6mg / kg), vehicle (sesame oil), METH + estrogen (1mg / kg), METH + progesterone (8mg / kg), and METH + estrogen + progesterone. Body temperature and anxiety-like behaviors were investigated, then, the animals were killed and brain tissues were harvested to evaluate brain edema and neuronal death in hippocampal CA1. Results: Body temperature, brain water content, motor activity, and anxiety-related behaviors significantly increased in animals that received METH (P<0.001), but, treatment with estrogen and progesterone attenuated motor activity, and anxiety-related behaviors induced by METH. Brain edema, body temperature, and neuronal cell death in hippocampal CA1 area partially decreased in METH+estrogen and METH + progesterone groups. Conclusion: This study suggests that ovarian hormones such as estrogen and progesterone are effective in improving behavioral deficits and neuronal death induced by METH in ovariectomized rats.