Characterizing Addiction Pathways
Multi-level testing of the cortico-basal ganglia-thalamic circuit to identify distinct addiction causation
Classical methods of addiction treatment have focused on addressing acute symptoms, such as withdrawal and craving cessation, rather than identifying and reversing the underlying factors leading to addiction onset. Individuals who engage in addictive substance abuse continue to be at high risk for relapse long after interventions have been made, making ongoing behavioral management critical for effective treatment. Understanding the underlying factors that trigger both initial addiction onset and future relapse is a missing key to recovery in predisposed individuals.
Dr. Ferguson and her team have the overall goal of using a multi-level approach to understand the role of cortico-basal ganglia-thalamic circuitry in the development of behaviors that are associated with drug reward and addiction by combining molecular biology, anatomy and behavioral neuroscience. Her group similarly examines the processes that underlie decision-making, motivation and impulsivity and how factors, such as extended exposure to sensory stimulation, modulate the development of these behaviors. To accomplish these goals, the lab employs novel molecular-genetic approaches that use viral vectors to express engineered artificial receptors (DREADD receptors) or ion channels (optogenetics) in discrete cell populations and subcomponents of pathways in rodents. When activated by a synthetic ligand (clozapine-N-oxide) or light, these receptors/channels will transiently alter activity of selected cell populations. These neuronal manipulations can be paired with specific phases of behaviors (such as drug-induced locomotor sensitization, drug self-administration, and operant learning tasks) in order to parse out the neural circuitry that contributes to behaviors associated with addiction and other neuropsychiatric disorders.
Understanding the underlying pathways that lead to addiction onset and continued management is central to Ferguson’s objectives. Her work will continue to emphasize establishing a framework that can map the neural circuits of behaviors across disease states with the ongoing objective of creating improved outcomes for addiction patients. Furthermore, she is interested in collaborating with industry partners to leverage her rodent models towards developing new addiction treatments and diagnosis criteria.
Stage of Development
- Pre-clinical in vivo
- Collaborative research opportunity
- Sponsored research agreement
- Consultation agreement
- Yager LM, Garcia AF, Donckels EA, Ferguson SM. Chemogenetic inhibition of direct pathway striatal neurons normalizes pathological, cue-induced reinstatement of drug-seeking in rats. Addict Biol. 2018 Jan 5. [epub ahead of print]
- Ravinder S, Donckels EA, Ramirez JS, Christakis DA, Ramirez JM, Ferguson SM. Excessive Sensory Stimulation during Development Alters Neural Plasticity and Vulnerability to Cocaine in Mice. eNeuro. 2016;3
- Kerstetter K, Wunsch A, Nakata K, Donckels E, Neumaier J, Ferguson S. Corticostriatal Afferents Modulate Responsiveness to Psychostimulant Drugs and Drug-Associated Stimuli. Neuropsychopharmacology. 2016; 41: 1128-37.
- Ferguson S, Phillips P, Roth B, Wess J, Neumaier J. Direct-Pathway Striatal Neurons Regulate the Retention of Decision-Making Strategies. Journal of Neuroscience. 2013;33(28):11668-11676.
To learn more about partnering with Seattle Children’s Research Institute on this or other projects, email the Office of Science-Industry Partnerships.