Cocaine Addiction and the Role of Serotonin in Orbitofrontal Cortex Function

在过去的财政年度中，我们成功地记录了从大鼠脑切片中获得的OFC神经元，并研究了5-羟色胺（5-HT）对这些神经元的影响。 此外，我们已经确定，在接受自我注射可卡因训练的大鼠中，基线谷氨酸介导的突触传递存在缺陷，这种缺陷在训练结束后持续许多个月。 这种缺陷在OFC突触传递与巴甫洛夫过度期待行为任务，这是已知的依赖于完整的OFC功能的性能下降。 我们还发现，逆转这种缺陷可以恢复过度兴奋行为，支持OFC中突触功能改变是可卡因成瘾的主要结果的假设，这可能导致决策受损，更普遍的是认知。 目前的研究主要集中在5-HT在调节眶额皮层神经元活动中的潜在作用，以及可卡因的使用是否会改变这种活动。 这些实验将提供新的信息，5-HT在可卡因成瘾中发挥的作用，并在可卡因成瘾和戒断过程中表现出的决策受损。 此外，由于5-HT与几种神经精神疾病，如抑郁症，焦虑症，痴呆症，冲动-攻击性障碍（IAD），强迫症（OCD）和创伤后应激障碍（PTSD），这些实验应该提供有价值的信息，靶向5-HT系统在OFC作为潜在的治疗的临床效用。

During the past fiscal year we have successfully recorded from OFC neurons in brain slices obtained from rats, and have examined the effects of serotonin (5-HT) on these neurons. In addition, we have established that there is a deficit in baseline glutamate-mediated synaptic transmission in rats trained to self-administer cocaine that lasts for many moths after this training is finished. This deficit in OFC synaptic transmission was associated with decreased performance in a Pavlovian overexpectation behavioral task that is known to be reliant upon intact OFC function. We also found that reversing this deficit could restore the overexpectatio behavior, supporting the hypothesis that altered synaptic function in the OFC is a primary outcome of cocaine addiction, that may lead to impaired decision making, and more generally cognition. Current studies are now focused upon the potential role that 5-HT plays in regulating OFC neuron activity, and whther cocaine experience alters this activity. These experiments will provide novel information as to the role that 5-HT plays in cocaine addiction, and in the impaired decision-making exhibited during cocaine addiction and withdrawal. In addition, since 5-HT is linked to several neuropsychiatric disorders, such as depression, anxiety, dementia, impulsive-aggression disorder (IAD), obsessive-compulsive disorder (OCD), and post-traumatic stres disorder (PTSD), these experiments should provide valuable information as to the clinical utility of targeting the 5-HT system in the OFC as potential therapies.