Ph.D. (Doctor of Philosophy)
Department of Psychology
Healthy individuals worldwide are using cognitive enhancing drugs in an attempt to remain competitive in society for education, careers, and athletics. Commonly, these individuals are using prescription stimulants, such as methylphenidate (MPH), due to their known acute neuroenhancing effects. While these neuroenhancing effects have been established using a variety of learning, memory, and attention tasks in humans and rodents, little research has investigated the effects of MPH use on specific components of these tasks, such as cue salience. One process that is important for learning the relationship between a cue and a reward is salience, or the heightened perception and desirability of cues associated with the reward. Salience toward cues can facilitate learning, but may also be implicated in increasing the likelihood of addiction and relapse. Cue salience is also related to dopamine D2 receptor function, which can be influence my MPH administration. In rats, salience toward cues can be quantified using the Pavlovian Conditioned Approach (PCA) Index. Heightened salience towards cues may also make shifting one’s attention away from one learned to cue to a novel cue more challenging. Many of MPH’s cognitive enhancing effects are attributed to enhancement of working memory; previous research shows that MPH enhances behavioral flexibility in an attentional set-shifting task in ADHD-diagnosed individuals. It is unknown whether prior exposure to MPH alters attentional set-shifting performance in healthy adults. The current study hypothesized that daily administration of MPH in healthy adult rats would increase cue salience, leading to a subsequent impairment of attentional set-shifting and hypothesized that cue salience and attentional set-shifting would be mediated by D2 receptor function. Daily administration of MPH tended to decrease lever pressing and PCA Index Scores, but had no effect on D2 receptor immunoreactivity. Overall, there was no effect of MPH or raclopride alone on the attentional set-shift, but raclopride administration had different effects in rats previously exposed to MPH. Raclopride significantly increased trials needed to reach criterion during the set-shift in rats that were previously administered MPH suggesting that MPH has lasting effects on D2 circuitry that do not manifest changes in executive functioning, unless challenged with a D2 receptor antagonist. The lasting changes are now hypothesized to be an up-regulation of D2 receptors due to our finding that MPH tends to decrease PCA Index Scores. Thus, when administered a D2 receptor antagonist, rats with upregulated D2 receptors may have dopaminergic function that is beyond an optimal performing range. These data suggest that cue salience may be a mechanism underlying the use of MPH for cognitive enhancement, which may also have implications for association mechanisms in addiction.
Mcwaters, Mercedes, "Investigating the effects of methylphenidate on cue salience and behavioral flexibility: Role of D2 receptors" (2019). Graduate Research Theses & Dissertations. 7427.
Northern Illinois University
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