Year: 2025
Type: dissertation
Abstract: The μ-opioid receptors (MOPr) are responsible for the effects of most opioid analgesics, including morphine. MOPr is expressed throughout the nervous system, particularly by nociceptors and other neurons involved in pain perception. However, there is now evidence that MOPr is also expressed in non-sensory neurons, but its role in these cells and its implication in the mentioned adverse effects are still largely unknown. En1 is a molecular marker expressed by V1 pre-motor neurons located in the ventral horn of the spinal cord that also expresses MOPr. Oprm1 is the gene which encodes MOPr. We used conditional knockout (cKO) mice to evaluate how the ablation of Oprm1 in En1-expressing neurons alters or affects behavior after morphine and whether it is related to pain or motor functions. The expression of Oprm1 in En1 neurons was confirmed with in situ hybridization. The behavior of the mice in which Oprm1 has been removed (En1Cre/+; Oprm1fl/fl) was phenotyped with von Frey filaments, hot plate test, raised beam test, and open field chamber to better understand its function. The morphine-induced hyperlocomotion was completely absent in the En1Cre/+; Oprm1fl/fl mice suggesting that the MOPr/En1 expressing neurons likely play a role in hyperlocomotor activity caused by morphine administration. There was a significant difference noted for fine motor coordination, suggesting that En1 is involved in more fine motor coordination tasks and balance. The absence of affective-emotional responses for the two mouse lines highlights the effects of morphine analgesia. The lower mechanical threshold for the cKO mice indicates that En1 may play a role in the mechanical analgesic properties of morphine.
DOI: 10.17615/h3rg-a412
Author: Saju, Jonathan
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W6943525715
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