Neuroprotective Effects of Berberine Hydrochloride on Methamphetamine-induced Cognitive Dysfunction: Immunohistochemical and Behavioral Studies in Rats

INTRODUCTION: Methamphetamine (MA) as an addictive psychostimulant drug affects the central nervous system. The current research aimed to evaluate the impact of berberine hydrochloride on improving cognitive function and neuroprotective effects in rats addicted to MA. METHODS: In this study, 27 male Wistar rats were randomly assigned to three groups, including control, MA addiction, and MA addiction with berberine hydrochloride (100 mg/kg/d) orally during the three weeks of withdrawal. Two groups received self-administered inhaled MA for two weeks (up to 10 mg/kg). Following the experimental procedures, a Morris water maze (MWM) and shuttle box were used to assess memory, and hippocampal sections from the animals were examined for caspase-3, Ki-67, and glial fibrillary acidic protein (GFAP) expression. RESULTS: The obtained results from the Morris water maze (MWM) showed that berberine hydrochloride decreases (P<0.01) the distance moved and the time spent to reach the hidden platform in the four-day learning trails phase and significant differences were observed in the distance moved, spent time, and frequency of motion in target quadrant on probe test day between groups. Berberine hydrochloride also reduced the latency of animals entering the dark chamber in the treated group compared to the control group (P<0.05). A significant decrease in activation of caspases-3, higher percentages of Ki-67 expression, and an increase in glial fibrillary acidic protein (GFAP) expression of cells was observed in the addicted group compared to the berberine-treated and control groups (P<0.05). CONCLUSION: Administration of berberine hydrochloride for 3 weeks improves cognitive function in MA addiction and it has potential neuroprotective efficacy. HIGHLIGHTS: Methamphetamine (MA) as an addictive psychostimulant drug affects the central nervous system. The berberine hydrochloride effects on improving cognitive function and neuroprotective. No approved pharmacotherapy, as well as confirmed medication, is available to treat MA abuse. PLAIN LANGUAGE SUMMARY: Methamphetamine (MA) is known as a strong addictive stimulant with high addiction and no approved pharmaco-therapy, as well as confirmed medication, is available to treat MA abuse. The study on the long-term effect of MA exposure on cognitive function during an object recognition memory test showed cognitive dysfunction after MA exposure. Berberine can reduce induced amnesia, which can be due to the increased peripheral and central cholinergic neuronal system functions, in addition, the most important mechanism in the protective effect of berberine against amnesia is the inhabitation of inflammation; however, the berberine impact on cells should be more investigated.