RESUMO
In addition to the essential pharmacologi-cal effects of opioids,situational cues associated with drug addiction memory are key triggers for drug seeking.CircRNAs,an emerging hotspot regulator in crown genet-ics-play an important role in central nervous system-relat-ed diseases.However,the internal mediating mechanism of circRNA in the field of drug reward and addiction mem-ory remains unknown.Here,we trained mice on a condi-tional place preference(CPP)model and collected nucle-us accumbens(NAc)tissues from day 1(T0)and day 8(T1)for high-throughput RNA sequencing.qRT-PCR revealed that circTmeff-1 was highly expressed in the NAc core but not in the NAc shell,suggesting that it plays a role in addiction memory formation.Meanwhile,the reverse regulation of circTmeff-1 by adeno-associated viruses could both inhibit the formation of addiction mem-ory in the NAc core or shell.Subsequently,the GO and KEGG analyses indicated 21 that circTmeff-1 might regu-late the addiction memory via the MAPK and AMPK path-ways.These findings suggest that circTmeff-1 in NAc plays a crucial role in morphine-dependent memory for-mation.
RESUMO
Objective To investigate the changes of monoamine neurotransmitters of the brain in physical dependence induced by morphine in rats.Methods A physical dependent rat model was established with morphine in a gradually in creasing doses and the withdrawal syndrome was scored after naloxone precipitation.The conditioned place preference(CPP)in rats induced by morphine was used to investigate psychic dependence in rats.Contents of norepinephrine(NE0,dopamine(DA)and serotonin(5-HT)in hypothalamus of rats were assayed with a fluorescent method. Results (1)In naloxone-precipitated withdrawal test of morphine-dependent model rats,after morphine had been withdrawn,morphine-abstinent rats presented marked withdrawal symptoms and signs,their withdrawal scores were significantly increased,and the levels of NE and 5-HT in the rat brain were obviously enhanced,but the content of DA was reduced.(2)In CPP test,morphine caused a marked place preference in rats and the levels of DA and 5-HT in the rat brain were obviously enhanced,but the content of NE was reduced.Conclusiion Morphine dependence development and withdrawal are closely connected with monoamine neurotransmitters in CNS.In the physical dependent model induced by morphine in rats,the rising of NE and 5-HT in the rat brain were significant,but in psychic dependent model induced by morphine in rats,the levels of DA in the rat brain were enhanced p-redominately.
RESUMO
Objective To investigate the changes of monoamine neurotransmitters of the brain in two tat models of morphine dependence,and to explore the effects of sinomenine on morphine dependence.Methods A physical dependent rat model was established with morphine at a gradually increasing dosage and the withdrawal syndrome was scored after naloxone precipitation.The conditioned place preference(CPP)in rats induced by morphine was used to investigate psychic dependence in rots.Contents of norepinephrine(NE),dopamine(DA)and serotonin(5-HT)in hypothalamus of rats were assayed with a fluorescent method.Results 1.In naloxone precipitated withdrawal test of in morphine-dependent rats,after morphine withdrawal,the rats presented marked with drawal symptoms and signs,their withdrawal scores were significantly increased,and the levels of NE and 5-HT in hypothalamus of the rats were significantly increased than the control group Ⅰ(7.07±1.406μg/g wet tissue and 1.15±0.346 μg/g wet tissue,respectively,P<0.01),but the content of DA was markedly reduced than the control group Ⅰ(0.28±0.121 μg/g wet tissue,P<0.05).2.In CPP model,morphine caused a marked place preference in rats and the levels of DA and 5-HT in hypothalamus were significantly increased than the control group Ⅱ(1.13±0.359 μg/g wet tissue and 1.23±0.343μg wet tissue,respectively,P<0.01),but the content of NE was not significantly changed(3.28±1.098 μg/g wet tissue,P>0.05).Sinomenine could significantly inhibit the withdrawal syndrome and development of CPP induced by morphine in rats,and could suppress the rising of monoamine neurotransmitters of the brain in two morphine dependent models in rats.Conclusion In the physical dependent model induced by morphine in rats,the rising of NE and 5-HT in the rat brain were significant,but in CPP model induced by morphine in rats,the levels of DA in the rat brain were enhanced predominately.Sinomenine could inhibit the withdrawal syndrome and development of CPP in rats,and regulate and improve the function of monoamine nerve system.