Effects of thyroliberin on mammalian neurotransmitter biochemistry

Hedley, Douglas (1982) Effects of thyroliberin on mammalian neurotransmitter biochemistry. PhD thesis, University of Glasgow.

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Thyroliberin (TRH) has been shown in a number of laboratories to have behavioural effects in animals unconnected with its endocrine function. Pharmacological studies have suggested the involvement of dopaminergic neurones in some of the observed effects and cholinergic neurones in others. Many of the behavioural effects of TRH in rodents appear to originate in the nucleus accumbens and septum brain regions. In this thesis the effects of TRH, one of its metabolites (cyclo HisPro) and a TRH-analogue (CG3703) on the release of dopamine and acetylcholine from rat brain tissue preparations were investigated. TRH (10-6--10-3M) stimulated the release of (3H)-dopamine from tissue-cube and P2 preparations of rat nucleus accumbens and striatum in a manner sensitive to the pH (pH 6.5 > pH7.4) and composition of the incubation medium. Cyclo-HisPro (1mM) stimulated the release of (3H)-dopamine from P2 preparations of nucleus accumbens and striatum at pH 6.5 but appeared to be no more potent than TRH in its effects. CG3703 (10-6--10-3M) stimulated the release of (3H)-dopamine from tissue cubes of rat nucleus accumbens at pH 6.5 but not at pH 7.4. Neither TRH nor its analogues (0.1mM) had any consistent effect on the release of (3H)-acetylcholine or (3H)-choline from tissue cubes of nucleus accumbens or septum at pH 7.4. 50mM-KCl in all cases stimulated the release of (3H)-dopamine from tissue preparations of nucleus accumbens and striatum at pH 6.5 and 7.4 and of both (3H)-acetylcholine and (3H)-choline from nucleus accumbens and septum. These results suggest that the stimulation of release of dopamine by TRH arise from a direct intaraction of the peptide with dopaminergic neurones, not by a modulation of dopamine release caused by TRH affecting release of acetylcholine. The increased potency of cycloHisPro and CG3703 relative to TRH in behavioural paradigms may result from their resistance to degradation.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: R MS Vaughan
Keywords: Biochemistry, Neurosciences
Date of Award: 1982
Depositing User: Enlighten Team
Unique ID: glathesis:1982-73723
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jun 2019 08:56
Last Modified: 14 Jun 2019 08:56
URI: https://theses.gla.ac.uk/id/eprint/73723

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