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Background and Aim: Cholinergic system can affect the drug reward.We aimed to examine the roles of muscarinic acetylcholine receptor(mAChR) and nicotinic acetylcholine receptor (nAChR) in morphine-induced behavioral sensitization.Methods: For analyzing the roles of mAChR and nAChR in behavioral sensitization induced by morphine (5 mg/kg),five experiments were designed.Experiment 1 examined the effect of scopolamine(3,1,0.3,0.2,0.1,O.05mg/ kg) on locomotor activity when administrated alone.Experiment 2 further explored the effect of scopolamine on morphine-induced behavioral sensitization.Experiment 3 studied the effect of mecamylamine on morphine-induced behavioral sensitization.Experiment 4 and 5 explored the effects of scopolamine + huperzine A or mecamylamine + huperzine A on morphine-induced behavioral sensitization.To investigate the relationship between mAChR in NAc shell and the behavioral sensitization induced by morphine,another three experiments were designed.Experiment 6 tested the effect of scopolamine in NAc shell on context induce expression of sensitization.Experiment 7 examined the effects of scopolamine and huperzine-A in NAc shell on morphine priming expression of sensitization.Experiment 8 investigated the effects of co-microinfusion of scopolamine and huperzine-A on morphine priming expression of sensitization.Results : We found that only 0.05 mg/kg scopolamine did not affect locomotor activity when administrated alone.The other higher doses of scopolamine,especially 3 mg/kg scopolamine,all significantly enhanced locomotor activity.3 mg/kg scopolamine inhibited the development of morphine-induced sensitization.Mecamylamine did not affect morphine-induced behavioral sensitization.The co-administration of scopolamine + huperzine A or mecamylamine + huperzine A did not affect the development of morphine-induced behavioral sensitization.However,scopolamine,but not mecamylamine,reversed the acute attenuation of huperzine A on morphine-induced locomotor activity during the development phase,and reversed the inhibition of huperzine A on the expression of morphine-induced sensitization.We also found that (a) cholinergic M receptor antagonist scopolamine microinjected into NAc shell blocked context induced expression of conditional sensitization;(b) cholinesterase inhibitor huperzine-A,but not scopolamine,microinjected into NAc shell blocked morphine priming expression of sensitization;(c) Co-microinfusion of scopolamine and huperzine-A reversed the inhibitory effect of huperzine-A on morphine-priming sensitization.Conclusion: The mAChR might play a more important role in the morphine-induced locomotor activity and expression of morphine-induced behavioral sensitization.The receptor mechanism of mAChR and nAChR was relatively separate in morphine-induced sensitization.The cholinergic M receptors in NAc shell played different role in the expression of morphine-induced behavioral sensitization challenged by context and by morphine.