The Effects And Mechanisms Of Repetitive Transcranial Magnetic Stimulation On Methamphetamine-dependent Rats

Objective: To explore the effects and mechanisms of repetitive transcranial magnetic stimulation(r TMS)on the addiction of methamphetamine(METH).Methods: The effects of different r TMS pattern on the acquisition,extinction and reinstatement of METH-induced Conditioned Place Preference(CPP)in rats,and the correlation molecular changes were examined.Our research is divided into threemajor parts: Firstly,to explore the effect of r TMS on the acquisition of METH-induced CPP behavior in rats.In the conditioning phase,rats were given r TMS(high frequency / low frequency)pretreatment before METH administration,and then the CPP score was tested in testing phase.Meanwhile,the expression of GABA_B receptor in rat prefrontal cortex and dorsolateral striatum was examined by Western Blot.Secondly,to detect the effect of r TMS on the extinction of METH-induced CPP in rats.In the extinction phase,rats were given r TMS treatment for two days,and then the CPP score was tested.The expression of GABA_B receptor in rat prefrontal cortex and dorsolateral striatum was also examined.Finally,the effect of r TMS on the reinstatement of METH-induced CPP were studied.After the disappearance of CPP behavior,rats in experimental group were treated with r TMS for 1 day or 3 days,then the CPP reinstatement effect of rats in experimental group and control group was tested(induced by METH).Results:(1)Low-frequency(1 Hz)r TMS can inhibit the methamphetamine-induced conditioned place preference in rats,accompanied by the downregulation of the R1 subunit of the GABA_B receptor in the dorsolateral striatum.However,r TMS with high frequency of 10 Hz had no significant effect on the formation of CPP.(2)High-frequency r TMS(10 Hz)can promote the methamphetamine-induced extinction of CPP with the up-regulation of the R1 subunit of the GABA_B receptor in the dorsolateral striatum,and this effect can be blocked by the GABA_B receptor antagonist CGP35348.(3)Long-term high-frequency r TMS(10Hz)treatment can inhibit CPP relapse behavior,but short-term high-frequency stimulation did not have such effect.Conclusions: rTMS can ameliorate the addiction behavior of methamphetamine-addicted rats,and its effect may be related to the function of GABA_B receptor in dorsolateral striatum.