Investigation of protective effects of naloxone on aluminium trichloride-induced memory impairment of senescence-accelerated mice and its mechanism

Raosheng GU; Nan SHEN; Yanchun WANG; Wei LIU; Kuang REN

ABSTRACT

BACKGROUND:

The content of aluminium generally increases in the cerebral cells of patients with senile dementia. Aluminium poisoning in brain has inner link with senile dementia. Naloxone is the specific antagonist of opioid receptor, which can be applied in the treatment of senile dementia according to foreign reports.

OBJECTIVE:

To investigate protective effects of naloxone on aluminium trichloride-induced memory impairment of senescence-accelerated mice and its mechanism.

DESIGN:

Randomized controlled trial.

SETTING:

Jilin Medical College.MATERIALS The experiment was completed in Laboratory of Pharmacology of Jilin Medical College (formerly the Jilin Military Medical College) from February 2001 to February 2003. A total of 100 healthy adult Kunming mice were selected and randomly divided into 5 groups control group, model group, naloxone 0.1 mg/kg group, naloxone 0.3 mg/kg group and naloxone 0.9 mg/kg group, with 20 in each group. Except the control group, subcutaneous injection with 70 mg/kg aluminium trichloride was given to the mouse in each group once a day for continuous 7 days; besides this, intraperitoneal injection with 0.1, 0.3, 0.9 mg/kg naloxone was given to the mouse in naloxone groups and the same amount of physiological saline was given to the mouse in the control group.

METHODS:

The methods of jumping stand and escaping dark were conducted to detect learning ability and memory of mice. Meanwhile, the content of malondialdhehyde in liver and mono-amine oxidase B in brain of mice were also detect.MAIN OUTCOME

MEASURES:

① Results of jumping stand experiment of aluminium trichloride-induced model of senescence. ② Results of escaping dark experiment of aluminium trichloride-induced model of senescence. ③ Comparison of malondialdhehyde and mono-amine oxidase B among each group.

RESULTS:

① Results of jumping stand experiment of aluminium trichloride-induced model of senescence Compared withmodel group, the frequency of electric shocks suffered by aluminium trichloride mice and the amount of suffered animals within 5 minutes significantly decreased in control group and naloxone 0.1, 0.3, 0.9 mg/kg groups. The experiment was repeated 24 hours later, naloxone could significantly prolong the latency of the mouse jumping down from the platform for the first time (P ＜ 0.01).Meanwhile, naloxone could decrease the amount and the frequency of mist&es of aluminium trichloride mouse within 3 minutes (P ＜ 0.01). ② Results of escaping dark experiment of aluminium trichloride-induced model of senescence Compared with model group, the latency of aluminium trichloride mouse entering dark box was significantly prolonged and the frequency of electric shocks suffered by aluminium trichloride mice obviously increased in control group and naloxone 0.1, 0.3, 0.9 mg/kg groups (P＜0.01). ③ Comparison of malondialdhehyde and mono-amine oxidase B among each group Malondialdhehyde was more in model group than in naloxone groups (P＜0.01). Mono-amine oxidase B was more in model group than in the other groups (P＜0.01).

CONCLUSION:

Naloxone has protective effects on aluminium trichlorideinduced memory impairment of senescence-accelerated mice, which can improve learning ability and memory. The mechanism is probably relevant to the effects of decrease of mono-amine oxidase B and elimination of lipid peroxide.