{"id":{"repo_id":"adelaide","oai_identifier":"oai:digital.library.adelaide.edu.au:2440/122010"},"canonical_url":"https://search.dev.ndltd.org/etd/adelaide/oai:digital.library.adelaide.edu.au:2440/122010","repository":{"repo_id":"adelaide","name":"University of Adelaide","base_url":"https://digital.library.adelaide.edu.au/server/oai/request"},"display":{"title":"Exploring the Pharmacology of (+)-Naltrexone on Alcohol Reward and Anxiety Behaviours","abstract":"Reward and anti-reward are two key processes mediating occasional and long-term consumption of alcohol. Traditionally, neurons were thought to be the exclusive mediators of reward and anti-reward. However, emerging evidence has highlighted the importance of the neuroimmune system, specifically, an innate immune receptor (Tolllike receptor 4) in mediating these phenomena. Toll-like receptor 4 (TLR4) is a pattern recognition receptor that detects conserved molecular epitopes expressed on pathogens, danger molecules and drugs of abuse. In response to alcohol the downstream signalling pathways of TLR4 (MyD88 and TRIF pathways) are activated. This culminates in the expression of classical pro-inflammatory cytokines and type-one interferons respectively. These immune molecules act via multiple pathways to influence neuronal activity thereby altering alcohol-related behaviour. No study has currently examined the relative contribution of each signalling pathway to alcoholinduced reward and anti-reward behaviours. Therefore, the aim of this thesis was to investigate the role of the TLR4-TRIF pathway in mediating acute alcohol-induced reward; reward priming following acute alcohol exposure; and long-term alcoholinduced reward and anti-reward behaviours in mice. The studies presented herein demonstrate pharmacologically attenuating TLR4-TRIF signalling via (+)-Naltrexone; reduces behavioural markers of acute alcohol-induced reward such as conditioned place preference and two-bottle choice – an effect dependent on the time-of-day; prevents acute alcohol-induced sensitisation during adolescence and some but not all markers of reward-like behaviour later in life; and lastly, did not alter behavioural indices of reward and anti-reward behaviour following long-term alcohol consumption. Collectively, the results highlight the importance of the TLR4-TRIF pathway in mediating the acute, but not necessarily chronic effects of alcohol reward and antireward.","abstract_html":"Reward and anti-reward are two key processes mediating occasional and long-term consumption of alcohol. Traditionally, neurons were thought to be the exclusive mediators of reward and anti-reward. However, emerging evidence has highlighted the importance of the neuroimmune system, specifically, an innate immune receptor (Tolllike receptor 4) in mediating these phenomena. Toll-like receptor 4 (TLR4) is a pattern recognition receptor that detects conserved molecular epitopes expressed on pathogens, danger molecules and drugs of abuse. In response to alcohol the downstream signalling pathways of TLR4 (MyD88 and TRIF pathways) are activated. This culminates in the expression of classical pro-inflammatory cytokines and type-one interferons respectively. These immune molecules act via multiple pathways to influence neuronal activity thereby altering alcohol-related behaviour. No study has currently examined the relative contribution of each signalling pathway to alcoholinduced reward and anti-reward behaviours. Therefore, the aim of this thesis was to investigate the role of the TLR4-TRIF pathway in mediating acute alcohol-induced reward; reward priming following acute alcohol exposure; and long-term alcoholinduced reward and anti-reward behaviours in mice. The studies presented herein demonstrate pharmacologically attenuating TLR4-TRIF signalling via (+)-Naltrexone; reduces behavioural markers of acute alcohol-induced reward such as conditioned place preference and two-bottle choice – an effect dependent on the time-of-day; prevents acute alcohol-induced sensitisation during adolescence and some but not all markers of reward-like behaviour later in life; and lastly, did not alter behavioural indices of reward and anti-reward behaviour following long-term alcohol consumption. Collectively, the results highlight the importance of the TLR4-TRIF pathway in mediating the acute, but not necessarily chronic effects of alcohol reward and antireward.","abstract_has_math":false,"creators":["Jacobsen, Jonathan Henry Webster"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Mustafa, Sanam","Buisman-Pijlman, Femke","Hutchinson, Mark"],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017","date_published":"2017","updated_at":"2026-07-24T00:50:36Z","subjects":[],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2440/122010","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Mustafa, Sanam","Buisman-Pijlman, Femke","Hutchinson, Mark"]},{"key":"dc:creator","label":"Author","values":["Jacobsen, Jonathan Henry Webster"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2017"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/2440/122010"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Reward and anti-reward are two key processes mediating occasional and long-term consumption of alcohol. Traditionally, neurons were thought to be the exclusive mediators of reward and anti-reward. However, emerging evidence has highlighted the importance of the neuroimmune system, specifically, an innate immune receptor (Tolllike receptor 4) in mediating these phenomena. Toll-like receptor 4 (TLR4) is a pattern recognition receptor that detects conserved molecular epitopes expressed on pathogens, danger molecules and drugs of abuse. In response to alcohol the downstream signalling pathways of TLR4 (MyD88 and TRIF pathways) are activated. This culminates in the expression of classical pro-inflammatory cytokines and type-one interferons respectively. These immune molecules act via multiple pathways to influence neuronal activity thereby altering alcohol-related behaviour. No study has currently examined the relative contribution of each signalling pathway to alcoholinduced reward and anti-reward behaviours. Therefore, the aim of this thesis was to investigate the role of the TLR4-TRIF pathway in mediating acute alcohol-induced reward; reward priming following acute alcohol exposure; and long-term alcoholinduced reward and anti-reward behaviours in mice. The studies presented herein demonstrate pharmacologically attenuating TLR4-TRIF signalling via (+)-Naltrexone; reduces behavioural markers of acute alcohol-induced reward such as conditioned place preference and two-bottle choice – an effect dependent on the time-of-day; prevents acute alcohol-induced sensitisation during adolescence and some but not all markers of reward-like behaviour later in life; and lastly, did not alter behavioural indices of reward and anti-reward behaviour following long-term alcohol consumption. Collectively, the results highlight the importance of the TLR4-TRIF pathway in mediating the acute, but not necessarily chronic effects of alcohol reward and antireward."]},{"key":"dc:title","label":"Title","values":["Exploring the Pharmacology of (+)-Naltrexone on Alcohol Reward and Anxiety Behaviours"]}]}],"canonical_facts":{"dc:contributor.advisor":["Mustafa, Sanam","Buisman-Pijlman, Femke","Hutchinson, Mark"],"dc:creator":["Jacobsen, Jonathan Henry Webster"],"dc:date.issued":["2017"],"dc:description.abstract":["Reward and anti-reward are two key processes mediating occasional and long-term consumption of alcohol. Traditionally, neurons were thought to be the exclusive mediators of reward and anti-reward. However, emerging evidence has highlighted the importance of the neuroimmune system, specifically, an innate immune receptor (Tolllike receptor 4) in mediating these phenomena. Toll-like receptor 4 (TLR4) is a pattern recognition receptor that detects conserved molecular epitopes expressed on pathogens, danger molecules and drugs of abuse. In response to alcohol the downstream signalling pathways of TLR4 (MyD88 and TRIF pathways) are activated. This culminates in the expression of classical pro-inflammatory cytokines and type-one interferons respectively. These immune molecules act via multiple pathways to influence neuronal activity thereby altering alcohol-related behaviour. No study has currently examined the relative contribution of each signalling pathway to alcoholinduced reward and anti-reward behaviours. Therefore, the aim of this thesis was to investigate the role of the TLR4-TRIF pathway in mediating acute alcohol-induced reward; reward priming following acute alcohol exposure; and long-term alcoholinduced reward and anti-reward behaviours in mice. The studies presented herein demonstrate pharmacologically attenuating TLR4-TRIF signalling via (+)-Naltrexone; reduces behavioural markers of acute alcohol-induced reward such as conditioned place preference and two-bottle choice – an effect dependent on the time-of-day; prevents acute alcohol-induced sensitisation during adolescence and some but not all markers of reward-like behaviour later in life; and lastly, did not alter behavioural indices of reward and anti-reward behaviour following long-term alcohol consumption. Collectively, the results highlight the importance of the TLR4-TRIF pathway in mediating the acute, but not necessarily chronic effects of alcohol reward and antireward."],"dc:identifier.uri":["http://hdl.handle.net/2440/122010"],"dc:language.iso":["en"],"dc:title":["Exploring the Pharmacology of (+)-Naltrexone on Alcohol Reward and Anxiety Behaviours"],"dc:type":["Thesis"]},"updated_at":"2026-07-24T00:50:36Z"}