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Title: Studies of dynorphin and cholecystokinin release in the rat spinal cord : implications for opioid action
Author: Riley, Ruth Clare
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1996
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Although much is now known of the cellular actions of exogenous opiate drugs and of endogeneous opioid peptides, how these compounds modify interconnecting neuronal systems in the CNS is still poorly understood. The studies described in this thesis have addressed the latter by employing the antibody microprobe technique to investigate (a) the release of dynorphin A(1-8) in the spinal cord of the rat as inflammation develops in peripheral tissues, and (b) the release of cholectystoknin, a putative 'anti-opioid' neuropeptide, in the rat spinal cord following the administration of morphine. A dramatic increase in the spinal synthesis of prodynorphin derived peptides has been observed when inflammation develops in peripheral tissues. The functional significance of this increased synthesis is unclear and there have been no reports of the stimuli needed to produce dynorphin release in vivo of possible controls of such release. Microprobes bearing immobilised antibodies to the dynorphin A(1-8) derivative of prodynorphin, were inserted into the lumbar spinal cord of urethane anaesthetised normal rats and those with a peripheral inflammation, to determine whether dynorphins are being tonically released and how release is altered by manipulating the inflamed tissues. In the absence of any active peripheral stimulus the antibody microprobes detected minimal amounts of immunoreactive (ir)-dynorphin A(1-8) in two areas (lamina I and laminae IV-V) in the dorsal horn of the spinal cord of normal rats. With the development of unilateral ankle inflammation over 3 to 5 days, following subcutaneous injections of Freund's complete adjuvant, this was extended to the ventral horn of both sides of the spinal cord. Lateral compression of the ankles of the normal animals did not release ir-dynorphin A(1-8) during the period of stimulation, but this neuropeptide was detected in the ventral horn following the stimulus.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available