Study On The Anti-Morphine Addiction Of α-Conotoxin TxIB

Morphine has become the most widely abused drug in the world today,which not only increases the financial burden of the family,causes family conflicts,but also leads to the path of crime,endangers others,and increases the social instability and the cost of medical assistance.However,morphine has good clinical application value.Morphine is mainly used for postoperative analgesia,cancerous pain,relief of pain during myocardial infarction,neuropathic pain,dysentery and other aspects.However,the addictive nature and hazards of morphine should not be ignored.Long-term use of morphine can cause serious physical complications and mental illness.What’s more serious is that large dose of morphine can cause the death of drug addicts.However,there is currently a lack of effective methods and drugs to prevent withdrawal and relapse.Previous studies have shown that the acetylcholine system was closely related to drug abuse.Theα6β2*nicotinic acetylcholine receptors（n ACh Rs）were involved in the drug reward pathway,which is an important target for the treatment of drug addiction by regulating the dopamine reward pathway from the ventral tegmental area to the nucleus accumbens.Theα-conotoxin TxIB,discovered from the Conus Textile,was an antagonist ofα6/α3β2β3 n ACh R(IC₅₀=28 n M).Preliminary researches showed that TxIB has a good inhibitory effect on nicotine addiction.We will further study the effect of TxIB in morphine addiction,providing a theoretical and scientific basis for its use as an anti-dependence drug.In this study,we evaluated the anti-morphine addiction effect ofα-conotoxin TxIB by establishing the conditioned place preference（CPP）model.Spontaneous activity experiment,Morris water maze and elevated plus maze experiment were used to study the effects of TxIB on locomotor activity,spatial learning and memory,and anxiety-like behaviors in mice.The results showed that continuous injections of morphine at dose of 5 mg/kg could successfully induce CPP model.The morphine administration intervals of 24 hours and 48 hours could significantly increase the time spent in the drug-paired box.The CPP model of morphine group（24 h）could last for 5 days,while the morphine group（48 h）could last for 15 days.In the CPP acquisition and expression phase,high-dose TxIB could inhibit the establishment and expression of morphine induced CPP model by intracranial ventricle injection.The single and consecutive administrations of TxIB did not produce place preference or aversion.In the spontaneous activity experiment,the place navigation and spatial probe experiment of the Morris water maze,and the elevated plus maze experiment,there was no significant difference compared with control group after single and consecutive injections of TxIB.α-Conotoxin TxIB,a specific antagonist ofα6/α3β2β3 n ACh R,could inhibit the acquisition and expression of CPP induced by morphine,without affecting the motor ability,spatial learning and memory ability,and anxiety-like behavior in mice,which is expected to be a potential anti-addiction drug.