Strategies to Identify Therapeutic Opportunities in the Treatment of Addictive Disorders


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Addictive 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.



addiction, addictive disorders, binge eating, binge eating disorder, serotonin, 5-HT, 5-HT2C receptor, 5-HT2A receptor, WAY163909, lorcaserin, pimavanserin, insular cortex, insula, prefrontal cortex, protein interaction, DREADDs, designer receptors exclusively activated by designer drugs, behavioral pharmacology, cue reactivity, high fat food, motivation, progressive ratio, reward, neuropharmacology, psychopharmacology, neural circuitry, neuronal modulation, behavioral-guided therapy, drug repurposing, combined therapeutic approaches