Congcong He
Northwestern University, IL·Neuroscience
Cocaine is one of the most widely abused drugs. It drives reward, craving and relapse, yet no FDA-approved medicine reduces cocaine use or prevents relapse.
- Fields
Neuroscience
Pharmacology
Biology
- Topics
autophagy
cocaine addiction
substance use disorder
- Grants
- 1 known grant, through May 2027
What they work on
- Determine how Becn2 (Beclin 2) acting in dopamine neurons controls learning to take cocaine, dose response and reinstatement of cocaine seeking in mice, using knockout mice that lack Becn2 only in dopamine neurons.
- Define how Becn2 drives the breakdown of the dopamine D2 receptor, the receptor that dampens dopamine release, through its binding partner GASP1, using biochemical, imaging and cellular approaches.
- Test whether a ULK1–Vps34–Becn2 autophagy pathway operates in dopamine neurons to regulate cocaine reward behaviors, using genetic and drug-based inhibition of the upstream kinases ULK1 and Vps34.
- Measure how the autophagy pathway affects cocaine-induced dopamine build-up and the number of D2 receptors on striatal neurons, using UPLC/mass spectrometry profiling of neurotransmitters.
More about the research
This project asks whether autophagy, the cell's system for breaking down and recycling its own parts inside lysosomes (the cell's digestive compartments), helps decide how vulnerable an animal is to cocaine. The lab's earlier work in mice gives a starting point. A protein called Beclin 2 (Becn2) partners with Vps34, an enzyme that switches on autophagy, and this pair controls how cocaine reward behaviors are acquired. Mice lacking Becn2, either everywhere or only in dopamine-producing neurons, were protected from cocaine-induced hyperactivity, from learning to prefer a place linked to cocaine, and from self-administering the drug intravenously. A closely related protein, Becn1, did not have this effect.
Why it matters
There is no approved medication to reduce cocaine use or prevent relapse. By tying an autophagy pathway (ULK1–Vps34–Becn2) to dopamine receptor breakdown and cocaine reward, this work could point to new drug targets for treating cocaine addiction. The same pathway may also matter for other forms of drug abuse. Drugs that inhibit ULK1 or Vps34 already blunted cocaine responses in mice.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Eduardo Gallo
Fordham University, NY·Neuroscience
Test whether dopamine D2 receptors on cholinergic interneurons of the nucleus accumbens control impulsive choice, by using cell type-specific genetic tools in mice to both increase and decrease receptor levels and measuring performance on a delay discounting task.
Catherine Cahill
University of California-Los Angeles, CA·Neuroscience
Determine whether the dynorphin–kappa opioid receptor system in the central amygdala is necessary and sufficient for negative reinforcement, meaning opioid taking to relieve a negative state, in mouse models of chronic pain.
John Mantsch
Medical College of Wisconsin, WI·Neuroscience
Test whether chronic unpredictable stress reduces dendritic spines on D2 receptor–expressing prelimbic neurons that project to the nucleus accumbens core, causing sex-dependent set-shifting deficits in mice.
The school
Northwestern University: 71 labs on PI Pages, $1.3B a year on research, 536 research doctorates a year.
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