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The behaviors of humans and animals are dependent on neurotransmitters and hormones that affect attention, alertness, and associative learning. These include the hormone estrogen (which plays an interesting role in cognition and attentional processes) and the neurotransmitter orexin (involved in wakefulness, arousal and goal-directed behaviors). Here we evaluated the roles of orexin receptors and estrogen in Latent Inhibition (LI), a measure of attention and associative learning. Latent inhibition is a behavioral phenomenon in which an organism's ability to associate new meaning to a familiar previously inconsequential (pre-exposed) stimulus is reduced when compared to associating meaning to a novel stimulus (non pre-exposed) in a classical conditioning paradigm. We hypothesize that orexin and estrogen have synergistic effects on latent inhibition (LI). Two-month-old female mice (OXR2-KO and WT) underwent aseptic ovariectomies and subsequently received subcutaneous placebo or estrogen treatment throughout the 10-day test. The mice underwent shaping, pre-exposure, conditioning, re-baseline, and testing. During pre-exposure approximately half the mice were exposed to a tone, while the other half were not. This stimulus was later paired with a foot shock on the conditioning day for all animals. On test-day the reaction (freezing response) to the tone stimulus was measured for both pre-exposed and non-preexposed animals. With the unfortunate circumstances of the current pandemic and inability to adequately increase the sample size, the effect of group (non-pre-exposed and pre-exposed), genotype (OXR2-KO and WT), and treatment (estrogen vs. placebo), all failed to reach statistical significance. However, both KO and WT placebo-treated animals exhibited increased freezing in the non-pre-exposed condition when compared to the pre-exposed condition, indicating a trend towards a normal LI response. There exists a necessity to further clarify the roles that orexin and estrogen play in a latent inhibition paradigm.


Utah State University

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The Effects of Estrogen and Arousal on Latent Inhibition

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