Neural Mechanisms Of Berberine Antagonizing Addictive Drugs

Background and objectiveBerberine is an alkaloid with many pharmacological activities,which has been widely used in the treatment of various diseases.At present,several behavioral studies have shown that berberine may be a potential drug for the treatment of drug addiction,but its neural mechanism is still unclear.Mammalian ventral tegmental area(VTA)is a midbrain region.As a comprehensive center,it regulates the incentive and incentive effects of almost all addictive drugs.However,little is known about the effect of berberine on neurons in VTA brain area.The effects of berberine on dopamine(DA)and γ-The effects of aminobutyric acid(GABA)on neuronal discharge and synaptic function to reveal the possible mechanism of berberine in the treatment of drug addiction.Materials and Methods1.Experimental animals: C57 BL / J6 wild-type(WT)mice aged 2-7 weeks were used in this experiment.2.Preparation of brain slices containing VTA: brain slices containing VTA were prepared from the brain atlas of control mice 250 μM coronal section,used for the recording of brain patch clamp.3.Cell attachment pattern recording patch clamp and whole cell pattern recording: put the brain slices containing VTA under the phase contrast interference microscope,record the cell attachment pattern with the patch clamp under the high-power microscope,or record the electrophysiological data of DA neurons and GABA neurons in the ventral tegmental area in the whole cell pattern,and detect the effect of berberine on them.4.Data statistical analysis: software pclamp10.8 for patch clamp data acquisition and clapmfit 10.8 software for data analysis.Other software such as Excel,spss20,graphpad and prism8 are used for other data analysis.Paired t-test was used to analyze the data before and after administration.The data are expressed as mean ± standard error(mean± S.E.M.).Results1.Berberine can reduce the excitability of DA neurons in the VTA.2.Berberine can increase the frequency of inhibitory postsynaptic currents(sipscs)in DA neurons in the ventral tegmental area,but has no effect on the amplitude of sipscs.3.Berberine can improve the excitability of GABA neurons in the VTA.4.Berberine can reduce the frequency of inhibitory postsynaptic currents(sipscs)of GABA neurons in the VTA,but has no effect on the amplitude of sIPSCs.5.Berberine had no effect on the frequency and amplitude of excitatory postsynaptic currents(sIPSCs)of DA neurons and GABA neurons in the VTA.6.Berberine can increase the ratio of inhibitory postsynaptic currents(eipscs)induced by double pulse stimulation in GABA neurons in the VTA,suggesting presynaptic inhibition.7.Berberine can counteract the discharge weakening effect of GABA neurons in the VTA induced by nicotine.8.Berberine can reduce the effect of increasing the frequency of inhibitory postsynaptic current induced by nicotine in GABA neurons in the VTA.9.Berberine can reduce the effect of acetylcholine(ACh)-induced increased discharge frequency of GABA neurons in the VTA.Conclusion The experimental results show that berberine can inhibit the discharge activity of dopaminergic neurons in VTA area of mice.The mechanism may be that berberine can increase the inhibition of GABAergic neurons in VTA area by enhancing the discharge of GABAergic neurons in VTA area,and berberine can enhance the discharge of GABAergic neurons in VTA area through its presynaptic inhibition,which may be the neural mechanism of antagonizing a variety of addictive drugs.Berberine,which can enhance the inhibitory mechanism of GABAergic neurons in VTA region on DA neurons,has also been further verified in the removal of DA neuronal excitability caused by nicotine.