Role of Dopamine D2 Receptors in the Consolidation of Amphetamine-Cue Memory in Conditioned Activity in Rats

The neurotransmitter dopamine (DA) plays an essential role in reward-related incentive learning, whereby neutral stimuli gain the ability to elicit approach and other responses. In an incentive learning paradigm called conditioned activity, animals receive a stimulant drug in a specific environment over the course of several days. When then placed in that environment drug-free, they generally display a conditioned hyperactive response. Modulating DA transmission at different time points during the paradigm has been shown to disrupt or enhance conditioning effects. For instance, blocking DA D2 receptors before sessions generally impedes the acquisition of conditioned activity. To date, no studies have examined the role of D2 receptors in the consolidation phase of conditioned activity; this phase occurs immediately after acquisition and involves the stabilization of memories for long-term storage. To investigate this possible role, I trained Wistar rats (N = 108) in the conditioned activity paradigm produced by amphetamine (2.0 mg/kg, intraperitoneally) to examine the effects of the D2 antagonist haloperidol (doses 0.10, 0.25, 0.50, 0.75, 1.0, & 2.0 mg/kg, intraperitoneally) administered 5 min after conditioning sessions. Two positive control groups received haloperidol 1 h before conditioning sessions (doses 1.0 mg/kg and 2.0 mg/kg). The results revealed that post-session haloperidol at all doses tested did not disrupt the consolidation of conditioned activity, while pre-session haloperidol at 2.0 mg/kg prevented acquisition, with the 1.0 mg/kg group trending toward a block. Additionally, post-session haloperidol did not diminish activity during conditioning days, unlike pre-session haloperidol. One possible reason for these findings is that the consolidation phase may have begun earlier than when haloperidol was administered, since the conditioned activity paradigm uses longer learning sessions than those generally used in consolidation studies. Future studies may test if conditioned activity can be achieved with shorter sessions; if so, haloperidol would then be re-tested at an earlier time point. D2 receptor second messenger systems may also be investigated in consolidation. Since drug-related incentive stimuli can evoke cravings in those with drug addiction, a better understanding of the mechanisms of incentive learning may lead to the development of solutions for these individuals.

The roles of EFN-1 and seam cell V2 in the transmission of a stop cue for the posterior lateral microtubule in Caenorhabditis elegans

A functional nervous system requires the precise arrangement of all nerve cells and their neurites. To achieve this correct assembly, a myriad of molecular guidance cues works together to direct the outgrowth of neurites to their correct positions. The small nematode C. elegans provides the ideal model system to study the complex mechanisms of neurite guidance due to its relatively simple nervous system, composed of 302 neurons. I used two mechanosensory neurons, called the posterior lateral microtubule (PLM), to investigate the role of the ephrin and Eph receptor protein family in neurite termination in C. elegans. Activation of the C. elegans Eph receptor VAB-1 on the PLM growth cone is sufficient to cause PLM termination, but the identity and location of the activating ligand has not been established. In my thesis I investigated the ability of the ephrin ligand EFN-1 to activate VAB-1 to cause PLM termination when expressed on the same cell (in cis) and on opposing cells (in trans) to the receptor. I showed that EFN-1 is able to activate VAB-1 in cis and in trans to cause PLM termination. I also assessed the hypodermal seam cells as the source of the ephrin stop cue using fluorescently labelled and seam cell mutant transgenic worms. I found that although the PLM shows consistent termination on the seam cell V2 in wild type worms independent of PLM length, this process is not significantly disrupted in seam cell mutants. With this information I have created a new hypothesis that the PLM neurite is able the provide a positional cue for the developing seam cells, and have created a new transgenic strain which can be used to assess the impact of PLM and ALM cell ablation on seam cell position. My research is the first to demonstrate the ability of an ephrin ligand to activate its ephrin receptor in cis, and further research can investigate if this finding has in vivo applications.

Investigating Multiple Roles of Vocal Confidence in Persuasion

Although persuasion often occurs via oral communication, it remains a comparatively understudied area. This research tested the hypothesis that changes in three properties of voice influence perceptions of speaker confidence, which in turn differentially affects attitudes according to different underlying psychological processes that the Elaboration Likelihood Model (ELM, Petty & Cacioppo, 1984), suggests should emerge under different levels of thought. Experiment 1 was a 2 (Elaboration: high vs. low) x 2 (Vocal speed: increased speed vs. decreased speed) x 2 (Vocal intonation: falling intonation vs. rising intonation) between participants factorial design. Vocal speed and vocal intonation influenced perceptions of speaker confidence as predicted. In line with the ELM, under high elaboration, confidence biased thought favorability, which in turn influenced attitudes. Under low elaboration, confidence did not bias thoughts but rather directly influenced attitudes as a peripheral cue. Experiment 2 used a similar design as Experiment 1 but focused on vocal pitch. Results confirmed pitch influenced perceptions of confidence as predicted. Importantly, we also replicated the bias and cue processes found in Experiment 1. Experiment 3 investigated the process by which a broader spectrum of speech rate influenced persuasion under moderate elaboration. In a 2 (Argument quality: strong vs. weak) x 4 (Vocal speed: extremely slow vs. moderately slow vs. moderately fast vs. extremely fast) between participants factorial design, results confirmed the hypothesized non-linear relationship between speech rate and perceptions of confidence. In line with the ELM, speech rate influenced persuasion based on the amount of processing. Experiment 4 investigated the effects of a broader spectrum of vocal intonation on persuasion under moderate elaboration and used a similar design as Experiment 3. Results indicated a partial success of our vocal intonation manipulation. No evidence was found to support the hypothesized mechanism. These studies show that changes in several different properties of voice can influence the extent to which others perceive them as confident. Importantly, evidence suggests different vocal properties influence persuasion by the same bias and cue processes under high and low thought. Evidence also suggests that under moderate thought, speech rate influences persuasion based on the amount of processing.