Valerenic acid ameliorates amphetamine-related neurotoxicity by improving hypothalamus tyrosine hydroxylase and histamine-N-methyl transferase enzymes

Abstract

Background

Narcolepsy, obesity, and attention deficit hyperactivity disorder are all treated with amphetamine (a central nervous system stimulant) while valerenic acid (VA) has a pharmacological effect in the central nervous system.

Objectives

The purpose of this study was to ascertain whether VA is able to make amends for neurotoxicity by modifying hypothalamus expressions of the enzymes tyrosine hydroxylase and histamine-N-methyl transferase in rats orally administered with methamphetamine (METH).

Methods

There were thirty-six male albino rats split up into six equal groups, Control, VA (5 mg/kg)-treated, and VA (10 mg/kg)-treated groups: For four weeks, normal rats received oral administration of 1 ml of distilled water, 5 mg/kg of VA, and 10 ml/kg of VA once daily. METH-treated, VA (5 mg/kg) prior to METH-treated, and VA (10 mg/kg) before METH-treated groups: normal rats were oral administrated with METH (2.5 mg/kg), 3 days/week for 3 weeks, where the last two groups were oral administrated daily during four weeks at 5 mg/kg and 10 mg/kg VA, starting one week prior to METH administration.

Results

METH decreased superoxide dismutase, glutathione peroxidase, catalase, NADPH oxidase, interleukin-10, sucrose preference test, distance traveled test, and center square entries test, ATPase activity and the enzymes tyrosine hydroxylase and histamine-N-methyl transferase but increased malondialdehyde, conjugated dienes, oxidative index, serotonin, dopamine, norepinephrine, γ-aminobutyric acid, tumor necrosis factor-α, interleukin-1β, interleukin-6, nuclear factor kappa B levels, the center square duration test, tail suspension test, and forced swimming test. in the METH-treated animals' brain in contrast to the control group. After four weeks of oral administration of VA to METH-treated rats, all of these parameters returned to levels that were nearly control, indicating that a higher dose was more effective than a lower one.

Conclusion

VA ameliorated METH-related neurotoxicity by improving hypothamalus expressions of the enzymes tyrosine hydroxylase and histamine-N-methyl transferase.