Inhibitory brain signals in the side habenula involving specific receptors linked to depression-like behaviors in Parkinson’s disease models

Unilateral 6-hydroxydopamine lesions in rats led to depressive-like behaviors and hyperactivity of lateral habenula neurons.

• Loss of dopamine in the lateral habenula is associated with decreased GABA synthesis and release, as well as increased glutamate release.
• Injection of the GABA receptor agonist muscimol resulted in antidepressant-like effects and decreased LHb neuron firing rates.
• The GABA receptor antagonist picrotoxin increased the expression of depressive-like behaviors and raised LHb neuron firing rates.
• Lower doses of muscimol and picrotoxin were effective in lesioned rats compared to sham-operated rats.
• Muscimol increased serotonin release in the medial prefrontal cortex, while picrotoxin decreased serotonin release in both groups.
• Changes in GABA receptor transmission in the LHb may play a critical role in the regulation of Parkinson's disease-associated depression.

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