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Modulation of neurotransmitter amino acid release from the rat isolated spinal cord

Teoh, Hwee; (1995) Modulation of neurotransmitter amino acid release from the rat isolated spinal cord. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Behavioural and electrophysiological studies have demonstrated that aspartate, glutamate and γ-aminobutyric acid (GABA) as well as their receptors play primary roles in the regulation of nociception. An in vitro superfusion release model and autoradiographic methods have been used in the present work to further establish the relationship between these neurotransmitter systems within the dorsal horn of the rat spinal cord. In view of recent suggestions for GABAB receptor subtypes within the rat CNS, novel and established GABAB ligands have been used to characterise the GABAB receptors in the rat spinal cord. This has been carried out with electrical stimulation of dorsal roots attached to superfused hemisected isolated dorsal horn spinal cord slices. The data obtained provide marginal support for the suggestion that GABAB receptors regulating the release of glutamate and GABA in the region of the superficial dorsal horn may be different from each other. Results from release studies on the spinal cords of rats chronically treated with the GABAB agonist, (-)-baclofen, and the GABAB antagonists, CGP36742 and CGP56999A suggest that the spinal cord GABAB system is capable of functional plasticity. Release work on the spinal cords of rats neonatally treated with capsaicin concur with previous suggestions for the primary afferent origin of aspartate and glutamate but not GABA. Parallel autoradiographic studies to determine the synaptic localisation of glutamate and GABAB receptor binding sites in the substantia gelatinosa also agree with earlier reports on the presence of kainate, NMDA and GABAB receptors on the terminals of capsaicin-sensitive primary afferent fibres. In conjunction with the theme on nociception, the modulatory effects of morphine sulphate and lamotrigine on these neurotransmitter systems have been compared and contrasted. Results concur with previous reports on the possible specificity of lamotrigine for the glutamatergic system and suggest that this might be the mechanism via which lamotrigine exerts its antinociceptive properties.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Modulation of neurotransmitter amino acid release from the rat isolated spinal cord
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; GABA
URI: https://discovery.ucl.ac.uk/id/eprint/10103255
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