Nicholas Beacher Dissertation Defense
Contact Dr. Mark West for the WebEx link for this talk.
ABSTRACT OF THE DISSERTATION
DIFFERENTIAL NUCLEUS ACCUMBENS PROCESSING
OF REWARD CUES IDENTIFIED IN
“HIGH-RISK” VS. “LOW-RISK” GROUPS:
SUBSTANCE USE DISORDER
by NICHOLAS JAMES BEACHER
Dr. Mark O. West
Not all individuals that use drugs will develop substance use disorder (SUD), and identification of individuals predisposed to develop SUD is critical for preventative health management of this major health crisis. SUD is driven primarily by negative affect and reinforced by compulsive drug use even after years of abstinence. This devastating relapse component of SUD is thought to be influenced by intense drug craving episodes that can be triggered by drug associated cues. Such drug cues have been shown to reinvigorate previous drug associations that have been established in the mesolimbic dopamine system. The mesolimbic dopamine system is involved in regulation of natural reward seeking behaviors, but cocaine “hijacks” the natural reward system by elevating dopamine in key limbic processing regions such as the Nucleus Accumbens (NAc), in the presence of cues associated with drug use. The NAc is a focus of cue-associated SUD research because of “limbic-motor-integration.” The NAc shell subcomponent receives motivational signals from other limbic areas involved in rewarding activity. In turn, the NAc core processes information from shell and projects to premotor areas to guide the final motivated action. Researchers interested in identification of individual differences in cue-predisposition have used Pavlovian autoshaping as a way to isolate distinctive phenotypes; 1) Goal-Trackers (GT) approached the foodport 2) Sign-Trackers (ST) approached and attacked the CS and 3) A third group of animals that were neither Sign nor Goal-Trackers but were regularly omitted (the present study defined these as “Non-Trackers”, (NT)). ST were theorized to incentivize such reward cues, and have been studied as a phenotype predisposed to incentivize drug cues and have a higher likelihood of developing cue-induced relapse. Our experiment examined single NAc core and shell neuron changes in firing rate (FR) 200ms before and after the onset of a cue which signaled drug availability (tone-cue SD). We studied whether this tone-evoked activity was different for the same neuron when the tone resulted in a drug seeking response (Hits) compared to interdigitated trials in which the tone did not result in a Hit (Misses). We also explored how different phenotypes (ST, GT, and NT), and Intake groups (High Intake (HI), and Low Intake (LI)) influenced self-administration behavior, tone-discrimination, and NAc tone-processing differences between Hits vs. Misses. Results demonstrate that phenotype did not influence drug consumption or behavioral tone-discrimination, and that HI subjects in general were not likely to behaviorally discriminate the tone relative to LI subjects of the same group. HI groups that were actually able to discriminate the tone behaviorally showed corresponding strong tone-evoked processing differences on Hits vs. Misses in NAc shell neurons. HI groups that did not discriminate the tone behaviorally did not show these strong differences in NAc shell processing on Hits vs. Misses, a finding that unexpectedly was most prevalent among ST HI groups. Results do implicate ST as potentially a “high-risk” group with regard to cue-induced relapse, but other groups (GT, and NT) are at least as vulnerable to such risks and should always be included when studying phenotype differences in SUD.