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Habenular Neurons Expressing Mu Opioid Receptors Promote Negative Affect in a Projection-Specific Manner

Julie Bailly1, Florence Allain2, Eric Schwartz3

  • 1Douglas Research Center, Department of Psychiatry, McGill University, Montréal, Quebec, Canada.

Biological Psychiatry
|December 10, 2022
PubMed
Abstract

Insights

Stimulating mu opioid receptor (MOR) neurons in the habenula (Hb) promotes negative affect. These neurons contribute to anxiety and despair via distinct pathways, suggesting opioid inhibition may relieve negative states.

Area of Science:

  • Neuroscience
  • Neuropharmacology
  • Behavioral Neuroscience

Background:

  • The mu opioid receptor (MOR) is crucial for reward and hedonic balance.
  • MOR is highly expressed in the habenula (Hb), a key brain region for aversion.
  • Previous studies suggest MOR signaling in the Hb may limit aversive states.

Purpose of the Study:

  • To investigate whether MOR-expressing neurons in the habenula (Hb-MOR neurons) promote negative affect.
  • To elucidate the neural circuits through which Hb-MOR neurons mediate aversion.

Main Methods:

  • Utilized Oprm1-Cre knockin mice for targeted manipulation.
  • Combined anterograde tracing and optogenetics with behavioral assays (real-time place preference, open field, elevated plus maze, marble burying, tail suspension).

Main Results:

  • Optostimulation of Hb-MOR neurons induced avoidance behavior.
  • Hb-MOR neurons project to the interpeduncular nucleus and dorsal raphe nucleus.
  • Stimulating Hb-MOR/interpeduncular nucleus pathways caused avoidance and despair-like behavior.
  • Stimulating Hb-MOR/dorsal raphe nucleus pathways increased anxiety.

Conclusions:

  • Hb-MOR neurons facilitate aversive states through two distinct circuits: one mediating despair-like behavior and another mediating anxiety.
  • Inhibition of Hb-MOR neurons by opioids may alleviate negative affect, impacting hedonic homeostasis and addiction mechanisms.
Keywords:
AnxietyAvoidanceDespair-like behaviorHabenula circuitryOpioidsOptogenetics

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