Blocking specific receptors in the brain's lateral habenula may increase antidepressant-like effects in rats with dopamine-related brain damage

Lesions of the substantia nigra pars compacta in rats produced depressive-like behaviors, while blocking lateral habenula calcium-permeable AMPA receptors resulted in antidepressant-like effects.

• Intra-lateral habenula injection of the CP-AMPAR antagonist Naspm led to antidepressant-like effects in both sham-lesioned and lesioned rats, with lower effective doses in lesioned rats.
• Blockade of LHb CP-AMPARs reduced the firing rate of LHb neurons and increased dopamine and serotonin release in the medial prefrontal cortex in both groups.
• The duration of Naspm's effects on neuron firing and neurotransmitter release was longer in SNc-lesioned rats compared to sham-lesioned rats.
• Lesioning the GABAergic rostromedial tegmental nucleus decreased the number of excited dopaminergic neurons in the posterior ventral tegmental area and serotonergic neurons in the median raphe nucleus.
• The findings suggest that LHb CP-AMPARs play a role in regulating neuron activity and neurotransmitter levels associated with depressive-like behaviors.

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