We combine animal models of psychiatric illnesses with advanced neuroscience approaches, including imaging, chemogenetic and anatomical techniques, to identify targets for novel therapeutics to treat these diseases
Orexin as a Common Mediator of Stress and Reward in Addiction
The lateral hypothalamus houses a small population of neurons (~7000 in rats, ~50,000-80,000 in humans) that produce the neuropeptide orexin (also known as hypocretin). These orexin-producing neurons project broadly throughout the brain and accordingly underlie a range of behavioral and physiological processes. This project uses viral-mediated tracing and calcium imaging approaches in transgenic rats combined with neural manipulation approaches, including designer receptors (DREADDs), to better understand the precise circuits through which orexin neurons mediate stress and reward behaviors in addiction.
Binge Eating - Circuits and Mechanisms
Binge eating disorder (BED) shares several phenotypic similarities with drug abuse, including a loss of control over food intake and increased responsivity to food cues. This project seeks to examine how the same neural circuits that underlie compulsive drug-seeking – including those involving orexin neurons – might also contribute to the binge eating phenotype. We use a model of palatable food intake that recapitulates many of the endophenotypes observed in BED, and measure changes in food motivation using a behavioral economics approach. We combine these behavioral models with several neural imaging and manipulation approaches to unravel the circuits contributing to the compulsive nature of food-seeking in BED.
Orexin-Based Therapeutics for Addiction and Feeding Disorders
We have a longstanding interest in the potential clinical utility of orexin receptor antagonists. In a series of ongoing experiments, we are exploring the efficacy and safety profiles of orexin receptor antagonists in preclinical models of addiction and obesity/binge eating disorder. As part of this, we are testing several experimental compounds and exploring the repurposing of the dual orexin receptor antagonist suvorexant (Belsomra), which is currently approved for the treatment of insomnia.
Sleep Disruption in Addiction - Circuits and Mechanisms
An estimated 80% of patients with a substance use disorder have a comorbid sleep disorder. In this project, we use whole-body telemetric recordings (EEG, EMG) to characterize sleep disturbance in rats with a history of drug self-administration, combined with calcium imaging and viral-mediated tracing techniques to examine the activity of arousal networks. By better understanding how drugs of abuse disrupt sleep, we seek to develop novel treatments designed to normalize sleep through the cycle of addiction.
Image credit: kahasciences.com