Cannabinoid CB1 Receptor Activation Mediates the Opposing Effects of Amphetamine on Impulsive Action and Impulsive Choice 英文参考文献.docVIP

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Cannabinoid CB1 Receptor Activation Mediates the Opposing Effects of Amphetamine on Impulsive Action and Impulsive Choice 英文参考文献.doc

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Cannabinoid CB1 Receptor Activation Mediates the Opposing Effects of Amphetamine on Impulsive Action and Impulsive Choice 英文参考文献

CannabinoidCB1ReceptorActivationMediatesthe OpposingEffectsofAmphetamineonImpulsiveAction andImpulsiveChoice JoostWiskerke,NickyStoop,DustinSchetters,AntonN.M.Schoffelmeer,TommyPattij* DepartmentofAnatomyandNeurosciences,VUUniversityMedicalCenter,Amsterdam,TheNetherlands Abstract It is well known that acute challenges with psychostimulants such as amphetamine affect impulsive behavior. We here studied the pharmacology underlying the effects of amphetamine in two rat models of impulsivity, the 5-choice serial reaction time task (5-CSRTT) and the delayed reward task (DRT), providing measures of inhibitory control, an aspect of impulsive action, and impulsive choice, respectively. We focused on the role of cannabinoid CB1 receptor activation in amphetamine-induced impulsivity as there is evidence that acute challenges with psychostimulants activate the endogenous cannabinoid system, and CB1 receptor activity modulates impulsivity in both rodents and humans. Results showedthatpretreatmentwitheithertheCB1receptorantagonist/inverseagonistSR141716AortheneutralCB1receptor antagonist O-2050 dose-dependently improved baseline inhibitory control in the 5-CSRTT. Moreover, both compounds similarly attenuated amphetamine-induced inhibitory control deficits, suggesting that CB1 receptor activation by endogenously released cannabinoids mediates this aspect of impulsive action. Direct CB1 receptor activation by D9- Tetrahydrocannabinol (D9-THC) did, however, not affect inhibitory control. Although neither SR141716A nor O-2050 affected baseline impulsive choice in the DRT, both ligands completely prevented amphetamine-induced reductions in impulsivedecisionmaking,indicatingthatCB1receptoractivitymaydecreasethisformofimpulsivity.Indeed,acuteD9- THCwasfoundtoreduceimpulsivechoiceinaCB1receptor-dependentway.Together,theseresultsindicateanimportant, thoughcomplexroleforcannabinoidCB1receptoractivityintheregulationofimpulsiveactionandimpulsivechoiceas wellastheoppositeeffectsamphetami