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The Heinsbroek lab is interested in how changes in the function of of the ventral basal ganglia circuits that drive motivated behaviors are contributing to the development of substance use disorders. We are currently sponsored by the National Institute on Drug Abuse to examine the roles of neurons in the ventral pallidum during relapse to drug seeking. Our past research identified opposing contributions of GABAergic and glutamatergic neurons in this brain structure during relapse to drug seeking, and identified that these neurons are differentially interconnected with upstream and downstream structures implicated in relapse to drug seeking such as the nucleus accumbens and ventral tegmental area. We are also funded by the National Institute on Drug Abuse to investigate the therapeutic potential of novel psychedelics-derived compounds that promote synaptic plasticity. Main current research projects in the lab are described below:
Project I: Regulation of opioid use and relapse to opioid seeking by ventral basal ganglia circuits
Project I: Regulation of opioid use and relapse to opioid seeking by ventral basal ganglia circuits
Project II: Regulation of motivated behaviors by ventral basal ganglia circuits
Project II: Regulation of motivated behaviors by ventral basal ganglia circuits
Project III: Novel pharmacological therapeutics for opioid use disorder
Project III: Novel pharmacological therapeutics for opioid use disorder
Regulation of relapse to opioid seeking by ventral basal ganglia circuits
Regulation of relapse to opioid seeking by ventral basal ganglia circuits
The ventral basal ganglia are critically involved in regulating opioid use and relapse to opioid seeking, but the precise mechanisms by which these circuits act to drive or limit opioid use and opioid seeking remain elusive. A main focus of our lab is to characterize changes in driver and limiter populations of neurons and circuits that regulate opioid seeking. In addition, we are investigating the neural circuit mechanisms that drive choice for heroin versus food. We recently identified that GABAergic neurons in the ventral pallidum drive relapse to drug seeking, and that glutamatergic neurons limit drug seeking behavior during relapse. Current research is investigating the wider circuit mechanisms through which these populations of neurons mediate drug seeking behaviors and to characterize changes in their function produced by opioid self administration.
Regulation of motivated behaviors by ventral basal ganglia circuits
Regulation of motivated behaviors by ventral basal ganglia circuits
The interconnected neural circuits of the ventral basal ganglia have long been known to play a crucial role in the regulation of motivated behaviors. These circuits include the nucleus accumbens and ventral tegmental area dopamine system. However, the ventral pallidum (VP), which is densely interconnected with both regions has, until recently, received comparatively less attention. Novel studies show complex emotional information processing by VP neurons through the integration of information from a wide range of sources. Furthermore, VP neurons process both positive and negatively salience. Our lab studies distinct pallidal subcircuit contributions to motivated behaviors in response to rewarding and aversive stimuli.
Novel pharmacological therapeutics for opioid use disorder
Novel pharmacological therapeutics for opioid use disorder
Opioid misuse and overdose related deaths continue to rise worldwide and we are in urgent need of novel effective treatments for opioid use disorder. Drugs that promote neuroplasticity have recently re-emerged as powerful candidates for the treatment of a variety of psychiatric conditions, including substance use disorders. These psychoplastigenic drugs include ketamine (Spravato; esketamine) which was recently approved for the treatment of major depressive disorder, and classical psychedelics such as psilocybin, which was recently given "breakthrough therapy" status by the FDA. In collaboration with the labs of Dr. David Olson at UC Davis and Dr. Jamie Peters at the University of Colorado, Anschutz Medical Campus, we are currently investigating the therapeutic potential of novel psychedelic-derived compounds with more favorable side effect profiles for the reduction of relapse to opioid use disorders. One such compound, tabernanthalog (TBG), is derived from the power hallucinogenic drug ibogaine, but unlike its parent compound, TBG does not have cardiotoxic side-effects. This project aims to identify and characterize novel anti-relapse and plasticity-promoting drugs for the development of more effective treatments for substance use disorders . Other novel pharmacotherapeutic targets for the treatment of opioid use disorder being investigated within the scope of this collaboration include drugs targeting the kappa-opioid, serotonin and orexin systems.
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