Berberine hydrochloride improves cognitive deficiency through hippocampal up-regulation of neurotrophins following inhalant self-administration of methamphetamine

Objective(s): Chronic methamphetamine (METH) abuse is recognized as an important risk factor for cognitive impairment. A plant-based isoquinoline alkaloid, Berberine hydrochloride (BER), shows memory and cognition enhancement properties. Due to the aim of the present study which is to investigate the influence of BER administration on METH-induced cognitive deficits, we investigated neurotrophin signaling including brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) as a possible mechanism by which BER exerts its cognitive improvement influences. Materials and Methods: In this experimental study, thirty-two male Wistar rats were randomly classified into four groups, including non-treated control, intubated control, METH-inhaled, and METH-inhaled + BER-intubated. Rats in the METH-inhaled group underwent METH inhalation for ۱۴ days, and the BER-inhaled and BER-intubated rats were intubated (۱۰۰mg/kg) for the following three weeks. A novel object recognition task (NORt) was carried out on days ۳۶ and ۳۷. Rats were sacrificed for histological preparations after the behavioral tests. Neurotrophic factors, including GDNF and BDNF, were evaluated by immunofluorescence staining in the hippocampus. Results: This experiment indicated a dramatic improvement in cognitive deficits associated with chronic METH abuse (P<۰.۰۰۱). Furthermore, a significant decrease in the expression of both neurotrophins, GDNF (P<۰.۰۰۱) and BDNF (P<۰.۰۰۱), was observed in the METH-inhaled group compared with the METH-inhaled group treated with BER and non-treated control group. Conclusion: Activation of neurotrophic factors after BER administration resulted in improvement of METH-induced cognitive deficits. Therefore, BER may be considered a promising treatment for METH users who experience cognition deficits.

کلیدواژه ها:

Addiction ، Cognition ، substance abuse ، Neurotrophic factors ، Neuroprotective