LOCUS COERULEUS NOREPINEPHRINE IN ACTIVE AVOIDANCE AND REWARD SEEKING BEHAVIOR

Abstract

Cue driven behavior relies on the ability to appropriately respond to stimuli in the environment to obtain resources (food, water, etc.) or avoid threats/danger. This behavior is driven by a desire to achieve a beneficial outcome, to obtain something positive (reward seeking) or avoid something negative (active avoidance). Many brain regions and neuromodulatory systems are involved in active avoidance and reward seeking behavior including the noradrenergic system and the locus coeruleus, the major originator of brain wide norepinephrine. This dissertation aims to identify if the role of locus coeruleus and norepinephrine is the same in reward seeking vs. active avoidance behavior. We found that locus coeruleus and norepinephrine are differentially involved in active avoidance and reward seeking behaviors. We first probed the role of noradrenergic receptor activation using pharmacology during an operant active avoidance and reward seeking task in rats. Our results showed that norepinephrine acting on separate noradrenergic receptor subtypes influenced reward seeking and active avoidance in a distinct sex dependent manner. Norepinephrine acting on α1 and β receptors disrupted active avoidance behavior in males and females while reward seeking was only disrupted in males. We next characterized locus coeruleus neural activity at baseline prior to investigating task related activity. Locus coeruleus activity at baseline differed across some biological factors such as sex and age. Last, we investigated locus coeruleus neural activity during the active avoidance and reward seeking task. We found separate and distinct populations of LC neurons that responded during active avoidance vs reward seeking trials. Our findings support our hypothesis that locus coeruleus and norepinephrine are differentially involved in active avoidance and reward seeking. Although the behavior is the same and the outcome is positive in both cases, the valence of reward seeking vs active avoidance engages distinct components of the locus coeruleus-noradrenergic system at the nucleus itself and at efferent targets. Understanding the function of locus coeruleus and norepinephrine in these tasks will inform our understanding of how the noradrenergic system is involved in behaviors important to survival and will provide insight into how these systems may go awry.NIH F31-MH131348Doctor of Philosophy (Ph.D.)2026-09-0