| Summary: | 碩士 === 國防醫學院 === 海底醫學研究所 === 96 === Recently, studies found that using methamphetamine will result in the decrease of monoamine secretion and neuronal damage. After long-term use of methamphetamine, patients develop withdrawal syndrome as they suddenly quit the drug. Of note, several withdrawal syndromes are similar to clinical depression symptoms. Thus, studies have utilized withdrawal symptoms by long-term methamphetamine intake as an animal model of depression disorder. It is noted that, the therapeutic effects of antidepressants do not appear until 2 to 6 weeks of treatment. There is an agreement that antidepressants produce neurogenesis, and has been linked to the pathway of inflammation and neurotransmitter such as cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF).
The PPARγ (peroxisome proliferators-activated receptor γ) agonist, pioglitazone could decrease cell apoptosis via anti-inflammation mechanism in animal models of neurodegeneration disease. In this study, we set an animal model of depression by using long-term escalating dose of methamphetamine. We treated rats with 2 doses of pioglitazone (10 mg/kg/day) and 1 dose of P-MPPI (3 mg/kg/day) plus fluoxetine (5 mg/kg/day). We recorded the animal behaviors of Novelty-suppressed feeding (NSF). We observed the changes of CREB and BDNF protein in hippocampus and cell pattern changes in cortex by immunohistochemestry. our study results show that：
1. The delayed and decreased food-intact time and food-volume during Novelty-suppressed feeding (NSF) in the animal model of methamphetamine withdrawal syndromes, one as expected similar to the depression-like animal model. Treatments of pioglitazone or P-MPPI plus fluoxetine could improved these behaviors.
2. The pioglitazone or P-MPPI plus fluoxetine protected agonist neuronal damage.
3. Increased of the numbers of astrocyte were observed after shot-term of escalating methamphetamine, but not in long-term group, consistent with the resultsy treatments with P-MPPI plus fluoxetine.
4. The pioglitazone significantly inhibited the activity of microglia after 7 days after withdrawal from escalating dose of methamphetamine.
5. The protein level of CREB and BDNF were significantly increased after treatment P-MPPI plus fluoxetine in rats given 21 days escalating dose of methamphetamine.
Conclusion: depressive-like behaviors have been improved both in pioglitazone and P-MPPI plus fluoxetine groups. The neurogenesis may be increased by anti-inflammation pathway in the pioglitazone group and in the P-MPPI plus fluoxetine groups, at least in part via increased CREB and BDNF protein levels. Thus, anti-inflammation and neurogenesis strategy may be applied in the treatment of depressive disorder in the clinic.
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