Modulation of Behaviorally Relevant Circuits of Opioid Withdrawal

National Institute On Drug Abuse

Investigators

Abstract

The opioid epidemic is a public health crisis that requires the need of innovative scientific solutions. Previous studies have shown that chronic opioid exposure induces neuroadaptations that play role during drug withdrawal. Opioid withdrawal is characterized by extremely unpleasant physical and affective symptoms after the drug use is terminated. Individuals are therefore compelled to continue using opioids in order to avoid experiencing these symptoms. However, the neural circuits and synaptic mechanisms that dictate these negative symptoms are not well understood at the behavioral level. We proposed to investigate the influence of RMTg-VTA circuit on the expression of spontaneous opiate-withdrawal behaviors. First, we will use slice electrophysiology to investigate if RMTg inhibitory synaptic inputs to DA neurons of the VTA are altered in response to spontaneous opioid withdrawal. Subsequently, we are going to employ chemogenetics inhibition of RMTg inputs to VTA, to test if this pathway is recruited for the expression of negative symptoms associated with opioid-withdrawal. We hypothesize that the activation of the RMTg-VTA circuit will be necessary for the expression of physical and affective symptoms of opiate-withdrawal. With this experimental design we intent to provide insight to the synaptic mechanisms underlying the behavioral symptoms of opiate-withdrawal, which is known to be a key determinant for continued opioid use and a contributing factor for relapse.