Pilot Project Research Core

Summary Pilot Research Project Core The Pilot Research Project Core (PRP) provides grant support and advising services for scientists interested in advancing the field of substance abuse. The Pilot Core will encourage applications from early-stage investigators preparing for their first NIDA R01 proposal. The PRP will also work with applicants to match them with the many technical services offered by the Center Cores. The Pilot Core will also support scientists developing new technologies that advances addiction research. To these ends, we describe three pilot projects that are ready for support and illustrate the focus of the PRP. 1) Do interactions between chronic pain and opioid exposure reduce cognitive flexibility? Drug abuse often follows emotional and physical pain. Data from our group indicates that chronic pain reduces executive function which can contribute to relapse. We hypothesize that chronic pain and previous exposure to opioids will interact such that animals exposed to chronic pain and opioids will exhibit severely reduced executive function and show evidence for relapse. We will test this hypothesis using Behavioral Core facilities, utilizing instrumental tests of cognitive flexibility. These studies will provide key pilot data for a NIDA R01 proposal investigating interactions between addiction, chronic pain, and executive function. 2) Wireless Stimulation and Photometric Measurement of Neural Activity in Mice: Technologies for the selective stimulation/inhibition of neural subtypes are needed to establish the causal roles they play in addiction. Traditional approaches use tethers connected to the animal that disrupt behavior and impair assessment of addiction-associated behaviors. This project supports development of wireless technologies that integrate optogenetic stimulation and photometry for measurement of neural activity without disrupting natural animal behavior. We plan to use this device to stimulate and suppress neurons associated with addiction. These technologies would benefit the Analytical and Behavioral Cores by eliminating the need for tethers during measurement and stimulation. This project will use services provided by the Behavioral and Genetics Cores. 3) Simultaneous Measurement of Dopamine Release and Single-Unit Activity in Behaving Animals. Dopamine release supports learning by triggering neuroplastic changes in cortical and striatal circuits. Addiction may result from atypically large dopamine release that enhances learning of drug-associated cues. There is no direct evidence for this theory as few methods exist for the simultaneous measurement of dopamine release and single-unit activity. Our group developed such a system for use in anesthetized animals. The goal of this pilot proposal is to adapt this system for routine use in awake and behaving animals, and to determine if functional connections between neurons are enhanced by phasic dopamine release. Experiments will utilize services of the Behavioral Core and preliminary data will be used for a planned NIDA proposal.