Continued investigations of the neurophysiological basis of the role of the cells in the nucleus accumbens in cocaine substance abuse are proposed in this application to extend support of a research program previously incorporated in the NIDA Center for Substance Abuse at BGSM. Due to the success of this Project it can no longer be adequately supported within the Center and is being submitted as an R01 application to pursue a more extensive research program. The proposed research program is based on several prior findings regarding the activity of neurons in the rostral pole, shell and core of the nucleus accumbens recorded in rats during either appetitive (water) reinforcement or cocaine self-administration. Having determined in prior studies that there are differential firing patterns of accumbens neurons related specifically to different aspects of the reinforced behavioral response in both reinforcement contexts (water and cocaine), the current research plan will provide a means of further differentiating accumbens cell firing with respect to different types of reinforcers. This is a critical issue because it is not known whether some aspects of cocaine self-administration behavior is maintained by aversive as well as positive reinforcing stimuli. The studies proposed here will therefore make a thorough assessment of the firing characteristics and behavioral correlates (via spike-triggered digitized video) of the same accumbens neurons within 2 of 3 distinctly different operant reinforcement paradigms (appetitive, aversive and cocaine self-administration). In each of the three contexts the motor components of the response will be nearly identical, with the exception that the operant response (lever press) will be an avoidance or escape response in the aversive motivational paradigm. It is important that the same neurons in the accumbens be recorded in at least two of these three conditions in order to perform population analyses on moderate to large numbers (15-40) of accumbens cells within each paradigm. Ensemble analyses will be performed to extract facets of accumbens neural network organization specific to and or in common with each reinforcement context. These analyses will also be performed on spike-triggered digitized video images of behavioral sequences associated with each of the previously identified types of accumbens neurons. The program will provide important information regarding positive and/or negative motivational factors involved in cocaine self-administration.
| Deadwyler, Sam A; Hayashizaki, Seiji; Cheer, Joseph et al. (2004) Reward, memory and substance abuse: functional neuronal circuits in the nucleus accumbens. Neurosci Biobehav Rev 27:703-11 |
| Nicola, S M; Deadwyler, S A (2000) Firing rate of nucleus accumbens neurons is dopamine-dependent and reflects the timing of cocaine-seeking behavior in rats on a progressive ratio schedule of reinforcement. J Neurosci 20:5526-37 |
