Effect Of Cannabinoids And Opioids On Synaptic Transmiss

大麻素和阿片类药物对突触传递的影响

• 批准号: 6680417
• 负责人: Carl R Lupica
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6680417
• 关键词: GABA receptor; cannabinoids; endogenous opioid; evoked potentials; glutamate receptor; laboratory rat; neural transmission; nucleus accumbens; reinforcer; synapses; voltage /patch clamp

The nucleus accumbens (NAc) represents a critical site for the rewarding and addictive properties of several classes of abused drugs. Therefore, it is necessary to understand the actions of abused drugs such as marijuana ands its derivatives on physiology of this system. The NAc medium spiny GABAergic neurons (MSNs) receive innervation from other intrinsic MSNs, and glutamatergic innervation from extrinsic sources. Both GABAergic and glutamatergic synapses onto MSNs are inhibited by drugs of abuse, suggesting that this action may contribute to the rewarding properties of these drugs. To investigate the actions of cannabinoids (CBs) in the NAc, we performed whole-cell recordings from MSNs in rat brain slices. Accomplishments attributable to this project in the past year include the establishment of a chronic delta-9-tetrahydrocannabinol (THC) treatment paradigm that successfully resulted in tolerance to various pharmacological effects of THC. This tolerance was also noted in the diminished inhibition of field excitatory postsynaptic potentials (EPSPs)in the nucleus accumbens shell. These studies are currently continuing by measuring synaptic EPSPs in single cells, determining whether withdrawal can be precipitated through antagonist application, and whether this withdrawal can be observed at the synaptic level. Additional experiments to be performed this year will examine wheter endogenous cannabinoids can alter synaptic physiology in the nucleus accumbens, and whether these endogenously released cannabinoids can alter long-term synaptic plasticity in this brain structure.

伏隔核（NAC）代表了几类滥用药物的奖励和成瘾性能的关键位置。因此，有必要了解大麻等滥用药物的作用及其对该系统生理学的衍生物。 NAC培养基GABA能神经元（MSN）从其他固有的MSN接收神经，并从外部源来获得谷氨酸能神经。滥用药物抑制了GABA能和谷氨酸能突触，这表明这种行动可能有助于这些药物的奖励性质。为了研究NAC中大麻素（CBS）的作用，我们从大鼠脑切片中的MSN进行了全细胞记录。 过去一年中归因于该项目的成就包括建立了慢性Delta-9-四氢大麻酚（THC）治疗范式，该范式成功地导致了对THC各种药理作用的耐受性。在伏伏核壳中，对场兴奋性突触后电位（EPSP）的抑制减少了，这种公差也被发现。目前，通过测量单个细胞中的突触EPSP，确定是否可以通过拮抗剂的应用来戒断，以及是否可以在突触水平上观察到这种戒断。今年将要进行的其他实验将检查内源性大麻素可以改变伏隔核中的突触生理，以及这些内源性释放的大麻素是否可以改变这种大脑结构中的长期突触可塑性。