Wnt7a in Mouse Insular Cortex Contributes to Anxiety-like Behavior During Protracted Abstinence from Morphine

Area of Science:

• Neuroscience
• Addiction Research
• Molecular Psychiatry

Background:

• Protracted abstinence in opioid addiction presents significant challenges, including anxiety, which elevates relapse risk.
• The insular cortex (IC) is implicated in emotional regulation and drug-induced changes, but its specific role in protracted abstinence anxiety is unclear.

Purpose of the Study:

• To investigate the role of the insular cortex (IC) in anxiety-like behaviors during protracted morphine abstinence.
• To identify specific IC subregions and molecular mechanisms involved in this process.

Main Methods:

• Assessment of anxiety-like behavior and physical withdrawal symptoms in morphine-dependent mice at 28 days of withdrawal.
• Analysis of glutamatergic neuron activation in different IC subregions (medial, anterior, posterior).
• Lesioning of IC subregions using ibotenic acid (IBO) and evaluation of anxiety-like behavior.
• Measurement of Wnt7a expression in the medial IC and its modulation using adeno-associated virus (AAV) vectors.

Main Results:

• Significant anxiety-like behavior emerged after 28 days of morphine withdrawal, independent of physical symptoms.
• Increased glutamatergic neuron activation was observed specifically in the medial IC, not anterior or posterior regions.
• Lesioning the medial IC, but not other subregions, alleviated anxiety-like behavior.
• Wnt7a expression was upregulated in the medial IC during protracted abstinence, and its downregulation reduced anxiety-like behavior.

Conclusions:

• The medial insular cortex (IC) plays a critical role in mediating anxiety-like behavior associated with protracted morphine abstinence.
• Wnt7a signaling within the medial IC is a key molecular mechanism contributing to this anxiety.