Gut-brain axis: Central impact of gut peptides and metabolic drug on monoamine neurotransmission
type: CreativeWork
description: Gastrointestinal peptides like insulin and glucagon-like peptide are not only essential metabolic hormones but can also modulate important brain function, unrelated to feeding behaviour and glucose homeostasis. Different evidence suggests that these peptides, as well as synthetic insulin secretagogue such as tolbutamide, can affect cognition, motivation, addiction as well as neuronal survival. In this thesis, we have investigated in rats whether insulin, or the insulin-releasing agent tolbutamide, and the stable glucagon-like-peptide-1 (GLP-1) receptor agonist exendin-4 as well as putative GLP-1 congener geniposide, can affect the electrical activity of dopamine neurons in the ventral tegmental area (VTA) and of pyramidal neurons in the prefrontal cortex (PFC), using single-unit activity recording techniques. We have also investigated, whether these peptides can alter some dopamine-dependent behaviours such as, D-Amphetamine (a dopamine-releasing agent) -induced motor activity, quinpirole (a dopamine D2/D3 receptor agonist) and pramipexole (a dopamine D3 preferred receptor agonist) -induced yawning, pica eating and pelvic grooming activities, as well as phencyclidine ( an N-Methyl-D-aspartate receptor antagonist)-induced cognitive deficit. We also examined the pharmacological mechanism of these drugs on radiometric in vitro [DA] release and uptake assays and investigated whether GLP-1 can modulate the effect of diet modification in form of chronic sucrose intake on behavioural and electrophysiological parameters. Interestingly, in uptake assay, exendin-4 and insulin weakened dopamine D2/D3 agonist (pramipexole and quinpirole)-induced [DA] uptake which suggests a potential interaction with D2/D3 receptor signalling. In addition, insulin and tolbutamide similarly reduced basal [DA] in striatal synaptosomes. Our electrophysiological data shows that GLP-1 receptor activation can change the excitability of prefrontal cortex neurons, an effect that can be associated with …
abstract: Gastrointestinal peptides like insulin and glucagon-like peptide are not only essential metabolic hormones but can also modulate important brain function, unrelated to feeding behaviour and glucose homeostasis. Different evidence suggests that these peptides, as well as synthetic insulin secretagogue such as tolbutamide, can affect cognition, motivation, addiction as well as neuronal survival. In this thesis, we have investigated in rats whether insulin, or the insulin-releasing agent tolbutamide, and the stable glucagon-like-peptide-1 (GLP-1) receptor agonist exendin-4 as well as putative GLP-1 congener geniposide, can affect the electrical activity of dopamine neurons in the ventral tegmental area (VTA) and of pyramidal neurons in the prefrontal cortex (PFC), using single-unit activity recording techniques. We have also investigated, whether these peptides can alter some dopamine-dependent behaviours such as, D-Amphetamine (a dopamine-releasing agent) -induced motor activity, quinpirole (a dopamine D2/D3 receptor agonist) and pramipexole (a dopamine D3 preferred receptor agonist) -induced yawning, pica eating and pelvic grooming activities, as well as phencyclidine ( an N-Methyl-D-aspartate receptor antagonist)-induced cognitive deficit. We also examined the pharmacological mechanism of these drugs on radiometric in vitro [DA] release and uptake assays and investigated whether GLP-1 can modulate the effect of diet modification in form of chronic sucrose intake on behavioural and electrophysiological parameters. Interestingly, in uptake assay, exendin-4 and insulin weakened dopamine D2/D3 agonist (pramipexole and quinpirole)-induced [DA] uptake which suggests a potential interaction with D2/D3 receptor signalling. In addition, insulin and tolbutamide similarly reduced basal [DA] in striatal synaptosomes. Our electrophysiological data shows that GLP-1 receptor activation can change the excitability of prefrontal cortex neurons, an effect that can be associated with …
author: Omoloye, Adesina
license: https://dora.dmu.ac.uk/bitstreams/de939826-a574-429b-aaa2-07267829785f/download
date published: 2019-08
date modified: 2026-07-24T06:18:47Z
provider: De Montfort University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: De Montfort University