Effect Of Drugs of Abuse On Synaptic Transmission In Nuc

滥用药物对 Nuc 突触传递的影响

• 批准号: 7321052
• 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/7321052
• 关键词: Effect; Drugs; Abuse; Synaptic; Transmission

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, cocaine, and opioids 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 are utilizing 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, particularly cross-tolerance between delta-9-tetrahydrocannabinol, the active ingredient in marijuana, and opiates. This tolerance was noted as a diminished diminished capacity for inhibition of field excitatory postsynaptic potentials (EPSPs)in the nucleus accumbens shell by both cannabinoid and opioid agonists. These data appear to provide a mechanistic explanation for the often-observed interactions between opioid and cannabinoid systems in behavioral studies. Ongoing studies with Dr. Bruce Hope are also investigating the effects of repeated cocaine treatment on synaptic inputs to MSNs. To do this, we are using rats that express a fluorescent marker in a discrete population of MSNs as a result of cocaine sensitization. By visualizing these specific neurons in our slice preparation, we can perform electrophysiological recordings from these cells and assess the mechanisms supporting cocaine sensitization. These studies are ongoing, and additional data are to be presented at the 2005 Society for Neuroscience Annual Meeting.

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，可卡因和阿片类药物等滥用药物对该系统的生理学的作用。 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，我们利用大鼠脑切片中MSN的全细胞记录。在过去一年中，归因于该项目的成就包括建立慢性Delta-9-四氢大麻酚（THC）治疗范式，该范式成功地耐受了THC的各种药理作用，尤其是跨耐受性，尤其是跨耐耐受性，尤其是在Marijuana，Opiiateent和Opiateentient和Opiateentient和Opiiateent中的Delta-9-9-四氢甲醇之间的耐受性。该公差被认为是抑制大麻素和阿片类激动剂抑制场刺激后突触后电位（EPSP）的能力降低的能力。这些数据似乎为行为研究中阿片类药物和大麻素系统之间经常观察到的相互作用提供了机械解释。与布鲁斯·霍普（Bruce Hope）博士进行的正在进行的研究还正在研究重复可卡因治疗对MSN突触输入的影响。为此，我们使用的是可卡因敏化后，在离散的MSN群体中表达荧光标记的大鼠。通过在我们的切片制备中可视化这些特定的神经元，我们可以从这些细胞中进行电生理记录，并评估支持可卡因敏化的机制。这些研究正在进行中，并将在2005年神经科学会议上提供其他数据。