Orexin- and Drug-induced Potentiation of Dopamine Neurotransmission and Reward-related Behaviours

Thomas, Catherine S.

Orexin- and Drug-induced Potentiation of Dopamine Neurotransmission and Reward-related Behaviours

dc.contributor.advisor	Borgland, Stephanie, L.
dc.contributor.author	Thomas, Catherine S.
dc.contributor.committeemember	Trang, Tuan
dc.contributor.committeemember	McGrath, Daniel
dc.date	Winter Conferral
dc.date.accessioned	2021-08-04T22:24:34Z
dc.date.embargolift	2021-07-14
dc.date.issued	2021-01-14
dc.description.abstract	Mesolimbic dopamine (DA) plays a pivotal role in orchestrating numerous motivated behaviours, including seeking and consumption of rewards and the attribution of motivational (incentive) value to reward-related stimuli, such as food and drug cues. Repeated exposure to drugs of abuse produces enduring changes in mesolimbic DA neurotransmission, including potentiated responses to future drug experiences, known as sensitization. A prominent theory of addiction proposes that sensitization of mesolimbic DA by drugs of abuse renders individuals hypersensitive to the motivational properties of drug stimuli (i.e., incentive sensitization), allowing them to gain powerful control over behaviour and ultimately driving addiction. However, it remains unknown how rapidly incentive value can be attributed to drug cues, or if previous drug exposure potentiates cue-evoked mesolimbic DA and attribution of incentive value to drug cues. Furthermore, the hypothalamic neuropeptide orexin (Ox), is hypothesized to sculpt mesolimbic DA and guide reward-related behaviours, including the drug-induced sensitization. However, the effects of endogenous Ox release in the ventral tegmental area (VTA) on mesolimbic DA and reward - related behaviour remains to be characterized. Chapter 1 of this thesis critically evaluates literature regarding motivation and related neurobiology, the effects of drugs of abuse, current theories of addiction, and the influence of Ox. Chapters 2 and 3 of this thesis demonstrate that repeated exposure to drugs of abuse and orexin release in the VTA increase mesolimbic DA and reward-related behaviour. Firstly, pre-treatment with cocaine or the short-acting opioid remifentanil increases rapid attribution of incentive value to a cocaine or remifentanil cue. Secondly, remifentanil pre-treatment potentiates remifentanil-evoked and cue-evoked mesolimbic DA across a single Pavlovian conditioning session. Thirdly, endogenous Ox release in the VTA leads to place preference and increases motivated food-cue directed behaviour. Lastly, Ox release in the VTA potentiates electrically evoked mesolimbic DA. The significance, caveats, and wider implications of this work is discussed chapter 4.
dc.identifier.citation	Thomas, C. S. (2020). Orexin- and Drug-induced Potentiation of Dopamine Neurotransmission and Reward-related Behaviours (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.doi	http://dx.doi.org/10.11575/PRISM/39066
dc.identifier.uri	http://hdl.handle.net/1880/113700
dc.language.iso	en	en
dc.language.iso	English
dc.publisher.faculty	Graduate Studies	en
dc.publisher.faculty	Arts
dc.publisher.institution	University of Calgary	en
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.	en
dc.subject	Motivation
dc.subject	Addiction
dc.subject	Dopamine
dc.subject	Sensitization
dc.subject	Orexin
dc.subject.classification	Behavioral
dc.title	Orexin- and Drug-induced Potentiation of Dopamine Neurotransmission and Reward-related Behaviours
dc.type	doctoral thesis
thesis.degree.discipline	Psychology
thesis.degree.grantor	University of Calgary	en
thesis.degree.grantor	University of Calgary
thesis.degree.name	Doctor of Philosophy (PhD)