Format

Send to

Choose Destination
Nat Commun. 2018 Jul 13;9(1):2710. doi: 10.1038/s41467-018-04654-2.

Nicotine aversion is mediated by GABAergic interpeduncular nucleus inputs to laterodorsal tegmentum.

Author information

1
Committee on Neurobiology, University of Chicago, Chicago, IL, 60637, USA.
2
Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL, 60637, USA.
3
Interdisciplinary Scientist Training Program, University of Chicago, Chicago, IL, 60637, USA.
4
St. Louis College of Pharmacy, Center for Clinical Pharmacology and Division of Basic Research of the Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
5
Division of Basic Research, Department of Anesthesiology, Washington University Pain Center, St. Louis, MO, 63110, USA.
6
Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, 63110, USA.
7
Committee on Neurobiology, University of Chicago, Chicago, IL, 60637, USA. dmcgehee@uchicago.edu.
8
Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL, 60637, USA. dmcgehee@uchicago.edu.

Abstract

Nicotine use can lead to dependence through complex processes that are regulated by both its rewarding and aversive effects. Recent studies show that aversive nicotine doses activate excitatory inputs to the interpeduncular nucleus (IPN) from the medial habenula (MHb), but the downstream targets of the IPN that mediate aversion are unknown. Here we show that IPN projections to the laterodorsal tegmentum (LDTg) are GABAergic using optogenetics in tissue slices from mouse brain. Selective stimulation of these IPN axon terminals in LDTg in vivo elicits avoidance behavior, suggesting that these projections contribute to aversion. Nicotine modulates these synapses in a concentration-dependent manner, with strong enhancement only seen at higher concentrations that elicit aversive responses in behavioral tests. Optogenetic inhibition of the IPN-LDTg connection blocks nicotine conditioned place aversion, suggesting that the IPN-LDTg connection is a critical part of the circuitry that mediates the aversive effects of nicotine.

PMID:
30006624
PMCID:
PMC6045623
DOI:
10.1038/s41467-018-04654-2
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center