BIV-03: Effect of μ-Opioid Receptor Knockout on Fear Conditioning, Extinction, and Morphine-Analgesia

Our understanding of the biological mechanisms underlying fear, trauma, and the development of related disorders like post-traumatic stress disorder (PTSD) are incomplete.  Thus, the search for players in the game continues.  Among the brain regions identified as exhibiting maladaptive changes/activity in PTSD, the amygdala appears to serve an important role in the acquisition and expression of fear.  Within the amygdala, the basolateral nucleus (BLA) integrates sensory information, with the central nucleus (CeA) helping to initiate/regulate a subsequent behavioral response.  Between the BLA and CeA lie a subset of GABAergic neurons known as the intercalated interneurons (ITCs).  They serve to modulate signaling, primarily from the BLA to the CeA.  The result of this is inhibition of the CeA via ITC activation by the BLA.  These ITC neurons also express the inhibitory mu-opioid receptor (MOR) very densely, and thus are sensitive to both the endorphins/enkephalins and exogenous opioids.  Importantly, ITCs appear to play a significant part in fear extinction.  In this experiment, we sought to determine the role of ITC MORs in fear acquisition and extinction.  To do this, we utilized a Cre expression (Cre- or Cre+) dependent knockout (KO) of Oprm1 from FoxP2-expressing neurons (e.g., ITCs).  Our results show significant interactions between both genotype and day as well as sex and day.  The effects are such that Cre+ (KO) mice extinguish fear at a slower rate than Cre-, and female mice extinguish fear slower than male mice.  These results imply that ITC MORs are involved in fear extinction.  Additionally, we conducted a control experiment using a morphine analgesia test on the hotplate to confirm the specificity of our MOR KO in Cre+ mice.  There were no significant differences in latencies across groups, demonstrating no effect of MOR KO on morphine analgesia.

Presenter(s): Henry Beckett, Psychology and Neuroscience Major
Advisor(s): Jennifer Quinn, Department of Psychology
Amanda Reichert, Department of Psychology
Jacob Dowell, Department of Psychology

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