Heterogeneous development of drug abuse
Creators: name: Beacher, Nicholas J.
Publisher: name: No Publisher Supplied
Year: 2018

description: The ability to identify individual predispositions to abuse drugs is important for long-term prevention of drug addiction. Drug addiction is in part driven by negative affect and is reinforced by compulsive resumption of drug taking. This problematic nature of addiction is thought to be influenced by drug-craving, triggered by reinvigoration of previous drug-associated environmental and contextual cues (Ikemoto &amp; Wise, 2004). The mesolimbic dopamine system is vital for the regulation of goal-oriented behaviors, which include drug, food, gambling, and sexual seeking. Impairment of the dopaminergic system dramatically influences addictive tendencies among individuals. Cocaine, and other drugs, are able to “hijack” the reward system, and elevate dopamine in critical relay structures, such as the nucleus accumbens (Nac) which is a target of cue-associated addiction research because of its limbic-motor integration. Anatomically, the Nac is divided into core and shell subregions. Nac-core is “downstream” from the shell and is striatal-like, with projections to premotor areas which influence movements and goal-oriented behaviors through laterally spiraling striatal connections. The Nac shell is considered ‘upstream’ of the core and receives motivational input from the amygdala, hippocampus, and other limbic cortical processing regions.Addiction researchers are able to identify differences in cue-predisposition through Pavlovian autoshaping (or STGT), which identifies two distinctive behavioral phenotypes; 1) Goal-trackers (GT), who approached the reward-port and 2) Sign-trackers (ST) who approached/attacked the lever-CS. ST have been theorized to incentivize reward cues and thereby prone to develop compulsive behavioral disorders such as addiction while GT animals have been largely ignored or used as a control to ST in drug addiction modeling. Notwithstanding this historical focus, we found high intake GT abandon pre-drug tone-discrimination and compulsively seek drug in the absence of the cue, resulting in high rates of uncued maintenance drug seeking which drove their higher drug intake. High intake, but not low intake, GT lacked the ability to control their internal drug level, which escalated to the highest recorded levels of any group during Hits. Non-GT titrated their intake throughout the session, and their DL did not significantly fluctuate between Hits and Misses within session. Additionally, high intake GT Nac core and shell neurons that were ‘active’ during Hits become ‘silent’ during Misses in that same session, suggesting the Nac could influence motivation to seek large quantities of drug. No other group demonstrated these trends, and because addiction is known to impact people of all backgrounds, GT and Non-GT may be prone to develop two distinct formations of drug addiction based on their inherent phenotype (goal vs cue oriented). Specifically, GT may represent a distinct animal model of addiction, one in which intense drug seeking is not highly influenced by contextual cues, but one where an internal ‘urge’ to take drugs results in an inability to control their drug intake.