Electroacupuncture Alleviates Adolescent Cocaine Exposure-induced Abnormal Behaviors In Adult Mice

BACKGROUND AND AIMS:Adolescence represents a high risk period for drugs of abuse.The individuals that beginning their drugs of abuse during adolescent period often exibit anxiety or impulsive behaviors in their later life,some even persisting into adulthood,and increase the risk of mental disorders.The prelimbic cortex(PrL)is located in the middle and upper region of the dorsomedial prefrontal cortex(mPFC).It is not only an important target for the neurotoxicity of psychostimulant such as cocaine,but also has been implicated in processing of psychostimulants-related psychiatric disorders,including anxiety,depression and cognitive deficits.The ?-aminobutyric acid(GABA)is the main inhibitory neurotransmitter in the central nervous system,which plays an important role in regulating the neurons of balance between excitatory and inhibitory transmission(E/I).The microcircuits(GABA IN-PN)formed by GABAergic interneurons(GABAIN)and pyramidal neurons(PN)are crucial for the physiological function of PrL.Acupuncture has been widely used to treat brain disorders.Electroacupuncture(EA)could alleviate drug withdrawal syndrome(such as anxiety,depression)and drug addiction in clinical and experimental studies.The present study aims:(1)To explore the effects of adolescent cocaine exposure on the psychiatric and cognitive behaviors in adult mice.(2)To investigate the effects of adolescent cocaine exposure on the structure and function of PrL GABA IN-PN circuit in adult mice.(3)To study the intervention effect of EA on abnormal behaviors and PrL GABA IN-PN by adolescent cocaine exposure in adulthood.METHODS:By using adolescent cocaine exposure model,novel object recognition test(NOR)was used to assess cognitive behaviors in adult mice.Elevated plus maze test(EPM)and marble-burying test(MBT)were used to assess anxiety-like behaviors.Tail suspension test(TST)and forced swimming test(FST)were used to assess depression-like behaviors.The behavioral experiments were used to observe the impact of electroacupuncture at acupoint Baihui(GV20)and Yintang(GV29).Immunofluorescence and electrophysiological experiments were used to examine the number and activity of GABA IN and PN in the adult PrL.The effect of parvalbumin interneuron(PV IN)on adolescent cocaine exposure-induced abnormal behaviors in adult mice was assessed through chemical genetics.The molecules of GABAergic transmission system in the adult PrL were examined by using western blot.RESULTS:(1)Adolescent cocaine exposure enhanced the anxiety-like and depression-like behaviors in adult mice.EA or local blocking the activities of PV IN in PrL alleviated these abnormal behaviors.(2)Adolescent cocaine exposure increased the number and activities of GABA IN and PV IN,the expression of molecules of GABAergic system,but suppressed the activitiy of PN.(3)EA attenuated the enhancement of PrL GABA IN-PN microcircuits by adolescent cocaine exposure in adult mice.CONCLUSION:The disbalance of PrL GABA IN-PN microcircuits,especially the enhanced activities of PV IN,contributes to adolescent cocaine exposure-induced abnormal behaviors in adult mice.Electroacupuncture alleviates abnormal behaviors induced by adolescent cocaine exposure at least partially by ameliorating the deficits of GABAergic system.