Strategies to Identify Therapeutic Opportunities in the Treatment of Addictive Disorders

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dc.creatorPrice, Amanda Elizabeth
dc.creator.orcid0000-0001-7441-3543
dc.date.accessioned2020-07-20T15:44:40Z
dc.date.available2020-07-20T15:44:40Z
dc.date.created2020-05
dc.date.submittedMay 2020
dc.date.updated2020-07-20T15:44:40Z
dc.description.abstractAddictive disorders are a collection of maladaptive behaviors characterized by the uncontrolled use of a rewarding substance. These include substance use disorders, binge eating disorder, certain subtypes of obesity, gambling disorder, and internet gaming disorder. Each of these disorders share similar behavioral characteristics that may be motivated by common neural substrates and molecular mechanisms. This dissertation aims to elucidate some of the drivers of addictive behaviors and proposes four strategies to identify therapeutic opportunities in the treatment of addictive disorders, with a special emphasis on binge eating disorder. The current work demonstrates an association between high fat food binge intake and cue reactivity, both of which are modulated by insula activity. Further, the clinically-approved serotonin (5-HT) 5-HT2A receptor (5-HT2AR) antagonist/inverse agonist pimavanserin and 5-HT2CR agonist lorcaserin used alone or in combination demonstrate efficacy in suppressing measures of binge eating. Pharmacological studies further show that activation of the 5-HT2CR may suppress binge eating by decreasing the reinforcing and motivational properties of high fat food. Finally, a possible role for a 5-HT2AR:5-HT2CR protein interaction in the protection against addictive behaviors is proposed. This dissertation concludes by discussing possible routes of implementation of the present findings into clinical practice. The strategies discussed – neuronal modulation, behavioral-guided therapy, drug repurposing, and combined therapeutic approaches – offer great possibilities in the development of new therapeutic approaches in the treatment of addictive disorders.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/2152.3/11245
dc.subjectaddiction
dc.subjectaddictive disorders
dc.subjectbinge eating
dc.subjectbinge eating disorder
dc.subjectserotonin
dc.subject5-HT
dc.subject5-HT2C receptor
dc.subject5-HT2A receptor
dc.subjectWAY163909
dc.subjectlorcaserin
dc.subjectpimavanserin
dc.subjectinsular cortex
dc.subjectinsula
dc.subjectprefrontal cortex
dc.subjectprotein interaction
dc.subjectDREADDs
dc.subjectdesigner receptors exclusively activated by designer drugs
dc.subjectbehavioral pharmacology
dc.subjectcue reactivity
dc.subjecthigh fat food
dc.subjectmotivation
dc.subjectprogressive ratio
dc.subjectreward
dc.subjectneuropharmacology
dc.subjectpsychopharmacology
dc.subjectneural circuitry
dc.subjectneuronal modulation
dc.subjectbehavioral-guided therapy
dc.subjectdrug repurposing
dc.subjectcombined therapeutic approaches
dc.titleStrategies to Identify Therapeutic Opportunities in the Treatment of Addictive Disorders
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentNeuroscience
thesis.degree.grantorThe University of Texas Medical Branch at Galveston
thesis.degree.levelDoctoral
thesis.degree.nameNeuroscience (Doctoral)

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