OBJECTIVE To examine the effects of aquaporin 4(AQP4) on opioid addiction and underlie the mechanism behind it. METHODS(1) In the heroin-induced self-administration(SA) experiment,we explored the role of AQP4 on heroi...OBJECTIVE To examine the effects of aquaporin 4(AQP4) on opioid addiction and underlie the mechanism behind it. METHODS(1) In the heroin-induced self-administration(SA) experiment,we explored the role of AQP4 on heroin-induced psychological addiction. After the mice were trained to learn heroin-induced SA under a fixedratio1(FR1) reinforcement program for 7 d,we randomly switched the heroin doses to 0.00625,0.0125,0.025,0.05 or 0.1 mg·kg^(-1)per infusion to counterbalance assignment design. In the end,all mice underwent extinction training and reinstatement testing.(2) In oral sucrose self-administration,5% sucrose solution was used for the mice and the procedures were similar to heroin SA.(3) In morphine-induced hyperactivity test,mice were habituated in the test apparatus for 30 min and then were given saline(10 mL·kg^(-1),sc) or morphine(10 or 20 mg·kg^(-1),sc) to record the locomotion for 1.5 h.(4) For the in vivo microdialysis experiment,mice were surgically implanted with intracranial guide cannula into nucleus accumbens(AP +1.4 mm,ML ±0.9 mm,DV-3.8 mm from bregma). After 5 d of recovery from surgery,the mice were challenged by saline(10 mL·kg^(-1),sc)or morphine(10 mg·kg^(-1),sc),and then samples were collected every 20 min. RESULTS We found that AQP4 deletion had no effects on sucrose-seeking and sucrose-taking,but it significantly attenuated heroin-taking and heroin-seeking behaviors in heroin self-administration. Besides these,AQP4 deletion had no effects on basal level of locomotion,but dramatically decreased morphine-induced hyperactivity.Furthermore,the in vivo microdialysis studies showed that AQP4 deficiency inhibited morphine(10mg · kg^(-1),sc)-induced elevation of extracellular dopamine levels in nucleus accumbens in mice.CONCLUSION Our present findings demonstrate that AQP4 was potentially involved in the properties of opioid rewarding by inhibiting dopamine release in nucleus accumbens(NAc).展开更多
MicroRNA-132(miR-132), a small RNA that regulates gene expression, is known to promote neurogenesis in the embryonic nervous system and adult brain.Although exposure to psychoactive substances can increase miR-132 exp...MicroRNA-132(miR-132), a small RNA that regulates gene expression, is known to promote neurogenesis in the embryonic nervous system and adult brain.Although exposure to psychoactive substances can increase miR-132 expression in cultured neural stem cells(NSCs)and the adult brain of rodents, little is known about its role in opioid addiction. So, we set out to determine the effect of miR-132 on differentiation of the NSCs and whether this effect is involved in opioid addiction using the rat morphine self-administration(MSA) model. We found that miR-132 overexpression enhanced the differentiation of NSCs in vivo and in vitro. Similarly, speci?c overexpression of miR-132 in NSCs of the adult hippocampal dentate gyrus(DG) during the acquisition stage of MSA potentiated morphine-seeking behavior. These ?ndings indicate that miR-132 is involved in opioid addiction,probably by promoting the differentiation of NSCs in the adult DG.展开更多
Nigeria has a very high number of sickle cell disease (SCD) population with addition of 150,000 babies born annually with the disease. Early infant diagnosis and good care make many of these babies survive to adulthoo...Nigeria has a very high number of sickle cell disease (SCD) population with addition of 150,000 babies born annually with the disease. Early infant diagnosis and good care make many of these babies survive to adulthood. Severe pain requiring moderately strong or very strong analgesics is a common presentation of patients with Sickle Cell Anaemia. Paediatricians find ready usefulness of Opioids which are very useful for the painful episodes among these patients. Therefore, the chances of abuse and addiction to these medications become very high and constitute additional burden on the deficient manpower in the health sector. Opioid Use Disorder among Sickle Cell Disease patients has subtle presentation, so a high index of suspicion is required to make both the diagnosis and referral to treatment centres. In this review, the epidemiology, pain pathophysiology, behavioural and pharmacologic therapy have been re-examined.展开更多
文摘OBJECTIVE To examine the effects of aquaporin 4(AQP4) on opioid addiction and underlie the mechanism behind it. METHODS(1) In the heroin-induced self-administration(SA) experiment,we explored the role of AQP4 on heroin-induced psychological addiction. After the mice were trained to learn heroin-induced SA under a fixedratio1(FR1) reinforcement program for 7 d,we randomly switched the heroin doses to 0.00625,0.0125,0.025,0.05 or 0.1 mg·kg^(-1)per infusion to counterbalance assignment design. In the end,all mice underwent extinction training and reinstatement testing.(2) In oral sucrose self-administration,5% sucrose solution was used for the mice and the procedures were similar to heroin SA.(3) In morphine-induced hyperactivity test,mice were habituated in the test apparatus for 30 min and then were given saline(10 mL·kg^(-1),sc) or morphine(10 or 20 mg·kg^(-1),sc) to record the locomotion for 1.5 h.(4) For the in vivo microdialysis experiment,mice were surgically implanted with intracranial guide cannula into nucleus accumbens(AP +1.4 mm,ML ±0.9 mm,DV-3.8 mm from bregma). After 5 d of recovery from surgery,the mice were challenged by saline(10 mL·kg^(-1),sc)or morphine(10 mg·kg^(-1),sc),and then samples were collected every 20 min. RESULTS We found that AQP4 deletion had no effects on sucrose-seeking and sucrose-taking,but it significantly attenuated heroin-taking and heroin-seeking behaviors in heroin self-administration. Besides these,AQP4 deletion had no effects on basal level of locomotion,but dramatically decreased morphine-induced hyperactivity.Furthermore,the in vivo microdialysis studies showed that AQP4 deficiency inhibited morphine(10mg · kg^(-1),sc)-induced elevation of extracellular dopamine levels in nucleus accumbens in mice.CONCLUSION Our present findings demonstrate that AQP4 was potentially involved in the properties of opioid rewarding by inhibiting dopamine release in nucleus accumbens(NAc).
基金supported by grants from the National Natural Science Foundation(81471353 and 81771433)the National Basic Research Development Program of China(2015CB553500)the Science Fund for Creative Research Groups from the National Natural Science Foundation of China(81521063)
文摘MicroRNA-132(miR-132), a small RNA that regulates gene expression, is known to promote neurogenesis in the embryonic nervous system and adult brain.Although exposure to psychoactive substances can increase miR-132 expression in cultured neural stem cells(NSCs)and the adult brain of rodents, little is known about its role in opioid addiction. So, we set out to determine the effect of miR-132 on differentiation of the NSCs and whether this effect is involved in opioid addiction using the rat morphine self-administration(MSA) model. We found that miR-132 overexpression enhanced the differentiation of NSCs in vivo and in vitro. Similarly, speci?c overexpression of miR-132 in NSCs of the adult hippocampal dentate gyrus(DG) during the acquisition stage of MSA potentiated morphine-seeking behavior. These ?ndings indicate that miR-132 is involved in opioid addiction,probably by promoting the differentiation of NSCs in the adult DG.
文摘Nigeria has a very high number of sickle cell disease (SCD) population with addition of 150,000 babies born annually with the disease. Early infant diagnosis and good care make many of these babies survive to adulthood. Severe pain requiring moderately strong or very strong analgesics is a common presentation of patients with Sickle Cell Anaemia. Paediatricians find ready usefulness of Opioids which are very useful for the painful episodes among these patients. Therefore, the chances of abuse and addiction to these medications become very high and constitute additional burden on the deficient manpower in the health sector. Opioid Use Disorder among Sickle Cell Disease patients has subtle presentation, so a high index of suspicion is required to make both the diagnosis and referral to treatment centres. In this review, the epidemiology, pain pathophysiology, behavioural and pharmacologic therapy have been re-examined.
