Noble, Wendy Jane; (2003) Nociceptin and the OP4 receptor in the auditory system. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

The opioid receptor-like OP4 receptor and its endogenous ligand, nociceptin (NC), have recently been isolated. Evidence suggests that the NC system may modulate sensitivity of the auditory system (Nishi et al., 1997). The work presented in this thesis was undertaken to elucidate the role of the NC system in auditory function. NC is expressed in both central and peripheral auditory structures. Furthermore, levels of NC expression appear to correlate with the development and maturation of the auditory system, both in precocial and altricial animals, suggesting that nociceptin expression may be related to auditory stimulation. To explore this possibility further, NC expression was examined in models of altered afferent input. Results obtained suggest that NC is affected by the level of acoustic stimulation and may act via the olivocochlear efferent system to protect the cochlea from damage. Evidence also suggests that NC is involved in auditory plasticity as long-term alterations in NC expression were noted following unilateral deafening. A differential regional and developmental pattern of OP4 receptor splice variant expression was observed, suggesting that the level of receptor expression may be related to development of the auditory system and raising the possibility that different variants may play specific roles in each tissue. Pharmacological properties of the OP4 receptor were determined in an OP4 receptor-transfected CHO cell line. Peptides identified in this study were then used in in vivo physiological experiments. These have shown that NC antagonists are able to reduce the discharge rate of binaurally-stimulated inferior colliculus neurones in response to pure tones. In conclusion, it appears that the NC system may play an important regulatory role in the auditory system, working either directly or via inhibition of auditory neurotransmitters to modulate auditory sensitivity. These effects may be a result of NC receptor activation at the level of the organ of Corti and/or in more central auditory nuclei.

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