Tianeptine pretreatment for the neurotoxity of methamphetamine

Xue WANG; Mingsheng HUANG; Jing LI; Xueli SUN; Lin KANG; Suxia LI; Jiaxiu ZHOU

ABSTRACT

BACKGROUND:

Methamphetamine (MA) has neurotoxic effects to central nervous system. However, as the 5-hydroxytryplamine reuptake enhancer, it is uncertain that if there are protective effects of tianeptine to the damages of 5-hydroxytryp-taminergic neurons caused by MA.

OBJECTIVE:

To investigate the neurotoxicity of MA and the neuroprotective effects of tianeptine as well as the acting mechanism.

DESIGN:

Randomized case control study based on animals.

SETTING:

Animal research room and pathology research room of a university.MATERIALS The experiment was completed in the Experimental Animal Centre of Sichuan University and Molecular Pathology Laboratory of West China Hospital during June to August 2003. Totally 25 male Wistar rats were injected MA through abdominal cavity to build model. Methamphetamine was provided by National Institute for the Control of Pharmaceutical and Biological Products(NICPBP) while tianeptine was given by French Servier Company (Batch No. OE3086). The TUNEL testing kit was purchased from Boehringer Mannheim Company.

INTERVENTIONS:

There were one control group and four experimental groups(A, B, C, D). A group was used intraperitoneal injection of MA while B, C, D, groups were administered tianeptine 7 days, 4 days before and the same day of MA administration. Normal saline with same volume was injected into rats of control group. HE stain and silver stain were conducted after experiment to observe the morphologic changes of neurons. And TUNEL method was used to detect apoptotic cells.MAIN OUTCOME

MEASURES:

The HE stain and silver stain of brain tissue sections and counts of TUNEL positive neurons.

RESULTS:

MA could damage the axon and dendrite of neurons and the absorbance of silver positive cell was(50.74 ± 1.86) . It could also induce cell apoptosis while the apoptotic cell count every high power field was 29.26 ±4. 14. There were less apoptotic cells in the group with 7 days usage of tianeptine with the cell count of( 18.90 ± 1.60) per high power field.

CONCLUSION:

MA can cause neurotoxicity by inducing cell apoptosis.And giving tianeptine in advance can protect neurons.