Targeting a common pathway in alcohol and nicotine abuse
Alcohol and nicotine both activate the medial habenulo-interpeduncular pathway (mHb-IPN), triggering an aversive inhibitory motivational signal that limits drug intake. This pathway also mediates somatic and affective symptoms of withdrawal from alcohol and nicotine. Accordingly, we hypothesise that cholinergic projections within the mHb-IPN pathway represent a locus to identify novel pharmacotherapeutic targets to treat alcohol and nicotine co-abuse. Using an innovative multidisciplinary approach combining genetic interventions (ChAT-Cre mice and chemogenetics), in vivo imaging with functional manipulation of the pathway (fiber photometry plus chemogenetics), and molecular profiling (transcriptomics), we will interrogate our hypothesis and the underlying neurobiological mechanisms through three comprehensive aims.
Aims
- Characterise the role of mHb-IPN cholinergic neurons in somatic withdrawal from alcohol, nicotine, and combined alcohol and nicotine dependence.
- Define how withdrawal from alcohol, nicotine, and combined alcohol and nicotine dependence affects the mHb-IPN cholinergic pathway.
- Use single cell sequencing combined with retrograde tracing to assess molecular adaptations in defined mHb cells that project to the IPN associated with dependence/withdrawal from alcohol and nicotine.
Research team
Members
Kathleen Teng
Research Assistant
Stella Cardozo
PhD Student
Research group
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