The purpose of this research project is to assess the manner in which information processing in brain structures of nonhuman primates is re-organized by the introduction of and sustained exposure to cocaine as a reinforcer for complex cognitive tasks. It has long been implicitly assumed in analyses of human drug addiction that substances which are abused somehow take over normal reinforcement mechanisms in the brain, diverting such """"""""reward pathways"""""""" to the control of drug seeking activities. Using a well-characterized short-term memory/executive function paradigm (multi-object delayed match to sample [DMS] task) studies will determine how cognitive processing is affected by acute and longterm exposure to cocaine as a reinforcer in this task. This primate model of cognitive function has been characterized in recent PET imaging and electrophysiological recording studies from this laboratory. On the basis of that work three important brain regions, medial temporal lobe (MTL), dorsal prefrontal cortex (DPFC) and the dorsal and ventral striatum (D/VStr), shown to be engaged during task performance, will be assessed for effects of cocaine on cognitive processing.
Aim 1 will determine neuronal firing characteristics in these three brain regions associated with performance of the DMS task and will identify single neuron correlates of low vs. high cognitive load trials.
Aim 2 will examine how these neural correlates change when the task is performed for cocaine injections delivered as the trial reinforcer in comparison to normal appetitive (juice) rewards.
Aim 3 will extend the above analyses to animals that are repeatedly exposed to conditions in which cocaine and juice reinforcers are implemented in the same random manner during day-to-day testing for a period of six months in order to assess cumulative changes in DMS responding and associated neuronal correlates over a time period in which performance is sustained at criterion levels by both reinforcers.
The final Aim 4 will assess the effects of stress on cocaine vs. juice reinforced DMS performance and associated neural correlates of cognitive load (Aim 1), induced by a method of sleep deprivation perfected for nonhuman primates in this laboratory. Relevance: In a society that is evolving more and more toward increased stress and demand on its citizens the individual level of cocaine abuse is a major health care problem. Such behavior eventually results in inability of the addict to cope with the complex nuances of a complex technologically-based work place. Turning to drugs is a natural course of action for pressured, overworked and under employed personnel.How cocaine use advances to addiction in this context is directly related to effects on cognition, reasoning and decision making. Therefore understanding how cocaine modulates and gradually over time eliminates effective cognitive processing, as studied here, is of primary importance in the prevention of drug addiction.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Neurobiology of Motivated Behavior Study Section (NMB)
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Volman, Susan
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Wake Forest University Health Sciences
Schools of Medicine
United States
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Deadwyler, Sam A; Berger, Theodore W; Opris, Ioan et al. (2015) Neurons and networks organizing and sequencing memories. Brain Res 1621:335-44
Opris, Ioan; Fuqua, Joshua L; Gerhardt, Greg A et al. (2015) Prefrontal cortical recordings with biomorphic MEAs reveal complex columnar-laminar microcircuits for BCI/BMI implementation. J Neurosci Methods 244:104-13
Hampson, Robert E; Song, Dong; Opris, Ioan et al. (2013) Facilitation of memory encoding in primate hippocampus by a neuroprosthesis that promotes task-specific neural firing. J Neural Eng 10:066013
Porrino, Linda J; Hampson, Robert E; Opris, Ioan et al. (2013) Acute cocaine induced deficits in cognitive performance in rhesus macaque monkeys treated with baclofen. Psychopharmacology (Berl) 225:105-14
Opris, Ioan; Santos, Lucas; Gerhardt, Greg A et al. (2013) Prefrontal cortical microcircuits bind perception to executive control. Sci Rep 3:2285
Hampson, Robert E; Fuqua, Joshua L; Huettl, Peter F et al. (2013) Conformal ceramic electrodes that record glutamate release and corresponding neural activity in primate prefrontal cortex. Conf Proc IEEE Eng Med Biol Soc 2013:5954-7
Hampson, Robert E; Gerhardt, Greg A; Marmarelis, Vasilis et al. (2012) Facilitation and restoration of cognitive function in primate prefrontal cortex by a neuroprosthesis that utilizes minicolumn-specific neural firing. J Neural Eng 9:056012
Santos, Lucas; Opris, Ioan; Fuqua, Joshua et al. (2012) A novel tetrode microdrive for simultaneous multi-neuron recording from different regions of primate brain. J Neurosci Methods 205:368-74
Opris, Ioan; Hampson, Robert E; Gerhardt, Greg A et al. (2012) Columnar processing in primate pFC: evidence for executive control microcircuits. J Cogn Neurosci 24:2334-47
Marmarelis, V Z; Shin, D C; Song, D et al. (2011) Dynamic nonlinear modeling of interactions between neuronal ensembles using principal dynamic modes. Conf Proc IEEE Eng Med Biol Soc 2011:3334-7

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