Heath Schmidt
University of Pennsylvania, PA·Neuroscience
Opioid use disorder remains a major public health crisis, and even with approved medications many people relapse after detoxification. That gap motivates a search for entirely different drug targets in the brain circuits that drive drug taking and drug seeking.
- Fields
Neuroscience
Pharmacology
- Topics
opioid use disorder
amylin
oxycodone
- Grants
- 1 known grant, through Mar 2030
What they work on
- Define how amylin receptors on specific cell types, dopamine and GABA neurons of the ventral tegmental area and D1- or D2-receptor medium spiny neurons of the nucleus accumbens, control oxycodone self-administration and relapse-like seeking, using viral gene delivery in transgenic rats.
- Determine how amylin treatment changes calcium activity in these midbrain and striatal cell types in oxycodone-experienced versus drug-naive rats, combining viral targeting with in vivo fiber photometry during behavior.
- Map how oxycodone, alone and with amylin treatment, alters amylin receptor expression and other genes across every cell population of the ventral tegmental area and nucleus accumbens using single-nuclei transcriptomics.
- Test whether amylin's suppression of opioid taking and seeking can be separated from its effects on feeding and from oxycodone's pain-relieving action, by comparing doses that do and do not alter food intake and antinociception.
More about the research
This project pursues an unexpected candidate: amylin, a hormone-like signaling peptide best known for telling the body it has eaten enough. Pilot work in rats showed that giving amylin reduces self-administration of oxycodone, a prescription opioid, and reduces relapse-like drug seeking, at doses that do not change food intake and do not blunt oxycodone's pain-relieving effect. Activating amylin receptors directly in the brain's reward circuitry was enough to produce the same reduction.
Why it matters
Relapse after treatment remains common in opioid use disorder. If activating amylin receptors in reward circuits reliably reduces opioid taking and seeking without blocking opioid pain relief or suppressing eating, it would support testing amylin-like drugs, several of which exist as metabolic agents, in people with opioid use disorder, and would give drug developers a specific set of brain cell types to target.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Mary Kay Lobo
University of Maryland, Baltimore, MD·Neuroscience
Map cellular, synaptic plasticity and molecular changes in defined cell subtypes of the medial prefrontal cortex and nucleus accumbens in mice exposed to fentanyl during the equivalent of human gestation, from weaning through adolescence.
Elizabeth Mietlicki-Baase
University at Buffalo, NY·Neuroscience
Test whether activating amylin receptors in the ventral tegmental area suppresses rapid dopamine release in the nucleus accumbens core in response to fat in the mouth, measured with fast-scan cyclic voltammetry.
Giuseppe Giannotti
Washington State University, WA·Neuroscience·Early-career
Track the real-time activity of PVT neurons tagged with TRAP during spontaneous versus naloxone-precipitated withdrawal, using in vivo calcium imaging while rodents respond to heroin-linked cues.
The school
University of Pennsylvania: 90 labs on PI Pages, $2.2B a year on research, 750 research doctorates a year.
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