The Effect Of Activation Of Serotonin 5-HT_2C Receptor On Behavioral Sensitization And Naloxone-Precipitated Withdrawal Symptoms In Mice

Part I The Effect of Activation of Serotonin 5-HT2C Receptor on Behavioral Sensitization and Naloxone-Precipitated Withdrawal Symptoms in MiceObjective:The aim of this study was to explore the effect of pharmacological activation of serotonin 5-HT2C receptor (5-HT2CR) on behavioral sensitization and withdrawal symptoms in morphine-dependent mice.Methods:We used EthoVision Noldus video tracking system to record the effect of 5-HT2cR agonist lorcaserin on locomotor activities and behavioral performances in mice. We build the model of morphine induced behavioral sensitization and chronic morphine treatment induced dependence in mice. To explore the effect of 5-HT2CR activation on behavioral sensitization and withdrawal symptoms in morphine-dependent mice. The 5-HT2CR expressions in NAc, LC and VTA were explored on behavioral sensitization and morphine-dependent mice.Results:(1) 5-HT2CR agonist lorcaserin (0.125,0.25 or 0.5 mg/kg) alone did not alter the locomotor activities as determined by distance traveled and velocity.(2) 5-HT2cR agonist lorcaserin (0.5 mg/kg) obviously blocked the induction and expression of behavioral sensitization, but lorcaserin (0.125,0.25 or 0.5 mg/kg) did not affect the development of behavioral sensitization.(3) 5-HT2CR agonist lorcaserin (0.5,0.75 or 1.0 mg/kg) and clonidine (0.2 mg/kg) significantly attenuated naloxone precipitated withdrawal symptoms, including jumping, burrowing, body grooming, rearing, wet dog shakes, head shakes, paw licking, penile grooming, and scratch, but did not affect the digging body posture, facial grooming and extend significantly decreased the distance traveled and velocity.(4) 5-HT2cR antagonist SB 242084(1.0 mg/kg) prevents lorcaserin-mediated suppression of behavioral sensitization and naloxone-precipitated jumping behavior in morphine-dependent mice.(5) A significant increase in the 5-HT2CR expression in VTA in morphine sensitization mice. Similarly,5-HT2CR expressions in NAc, LC and VTA were increased in morphine withdrawal mice.Conclusion:Pharmacological activation of 5-HT2cR suppresses the induction and expression of behavioral sensitization induced by repeated morphine exposure. Ameliorated naloxone-precipitated withdrawal symptoms in morphine-dependent mice.5-HT2cR may be a novel target to develop therapeutic approach for the treatment of opioid addiction.Part Ⅱ The Effect of Activation of Serotonin 5-HT2C Receptor on Behavioral Sensitization and Naloxone-Precipitated Withdrawal Symptoms in MiceObjective:The aim of this study was to explore the effect of pharmacological activation of serotonin 5-HT2CR on behavioral sensitization and withdrawal symptoms in heroin-dependent mice.Methods:We used EthoVision Noldus video tracking system to record the effect of 5-HT2CR agonist lorcaserin on locomotor activities and behavioral performances in mice. We build the model of heroin induced behavioral sensitization and chronic heroin treatment induced dependence in mice. To explore the effect of 5-HT2CR activation on behavioral sensitization and withdrawal symptoms in heroin-dependent mice.Results:(1) Lorcaserin (0.5 mg/kg), clonidine (0.05 mg/kg), naloxone (5.0 mg/kg) alone did not alter the locomotor activities as determined by distance traveled and immobility.(2) Lorcaserin (0.5 mg/kg) obviously blocked the induction, development, expression of behavioral sensitization induced by repeated heroin exposure.(3) Lorcaserin (0.5 mg/kg) suppresses distance traveled and enhances immobility in naloxone-precipitated heroin withdrawal mice.(4) Lorcaserin (0.5 mg/kg) significantly attenuated naloxone-precipitated withdrawal symptoms, including jumping, paw licking. And lorcaserin treatment significantly suppressed jumping and paw licking by 46.8% and 40%, respectively.Conclusion:Pharmacological activation of 5-HT2cR suppresses the induction, development, expression of behavioral sensitization induced by repeated heroin exposure. Ameliorated naloxone-precipitated withdrawal symptoms in heroin-dependent mice.