Abstracts Category : Other

The role of the kappa opioid receptor system in forebrain dependent associative learning

by Ryan Michael Loh

The opioid receptor system has been shown, through various lines of evidence, to be involved in pain processing, addiction, and learning and memory. It has been previously established that the mu opioid receptor (MOR) is intimately involved in the acquisition and consolidation of memories. While these studies have provided valuable insight into the role of MOR in learning, researchers have recently begun to elucidate a role for the kappa opioid receptor (KOR) with learning. Previous reports have demonstrated that KOR and its ligands are capable of modifying complex learned behaviors in paradigms such as water maze and fear conditioning. While these studies have established an important foundation suggesting that KOR plays a role in learning and memory, clear evidence for, and an understanding of the mechanistic role of KOR in learning is still lacking. To explore the role of KOR in learning, we have used the associative learning paradigm whisker trace eyeblink (WTEB) conditioning.With WTEB conditioning animals are trained to associate a neutral conditioned stimulus (CS - whisker stimulation), following a stimulus free trace interval with a salient unconditioned stimulus (US periorbital shock). With successive CS-US paired presentations, the subject begins to elicit a conditioned response (CR - eyeblink) to the CS, prior to US onset. Acquisition for this paradigm has been demonstrated to be forebrain dependent as removal of either the hippocampus or the neocortex can either hinder, or entirely block acquisition of the association (Solomon et al., 1986, Moyer et al., 1990, Kim et al., 1995, Weiss et al., 1999, Takehara et al., 2002, Galvez et al., 2007).Using this paradigm, the following thesis outlines a series of experiments designed to examine opioid and specifically KOR involvement in forebrain dependent learning mechanisms. To do this we first demonstrated in Chapter 2 that a global opioid antagonist, naloxone,administered intraperitoneally effectively blocks acquisition of the WTEB association. Further examining this relationship, in Chapter 3, systemic and local somatosensory neocortical injections of the KOR specific antagonist, NorBNI, demonstrate that blocking KOR results in a similar impaired acquisition. Following this pathway downstream, Chapter 4 outlines a phasic property of KOR in WTEB conditioning, in that early-phase antagonism causes deficits in acquisition of the association, while late-phase antagonism causes deficits in memory consolidation. Lastly, Chapter 5 demonstrated a significant increase in the amount of the dynorphin precursor peptide prodynorphin (PD) in the somatosensory cortex during and immediately following WTEB training. Collectively, the findings presented in this dissertation outline a novel role for KOR in the acquisition and consolidation of forebrain dependent associative memories while, providing additional insight into the underlying neocortical mechanism mediating our ability to learn and consolidate information.Advisors/Committee Members: Galvez, Roberto (advisor), Galvez, Roberto (Committee Chair), Gulley, Joshua (committee member), Juraska, Janice (committee member), Llano, Daniel (committee member), Wickesberg, Robert (committee member).