Dopamine D4 receptors in the brain's reward control area influence depression-like behaviors through nerve signal changes in a Parkinson’s disease model

High doses of the Dreceptor agonist A412997 and antagonist L741742 increased depressive-like behaviors in rats with lesions in the substantia nigra.

• Intra-LHb injections of varying doses of Dreceptor compounds produced different behavioral responses in sham-lesioned rats.
• Only the high doses of A412997 and L741742 were associated with increased depressive-like behaviors in substantia nigra lesioned rats.
• Low doses of these compounds altered the activity of LHb neurons and the release of neurotransmitters in sham-lesioned rats, but not in lesioned rats.
• High doses affected neurotransmitter release and neuronal firing rates in both sham and lesioned rats, though not through the GABAergic rostromedial tegmental nucleus.
• Lesions in the substantia nigra shortened the duration of significant effects on neurotransmitter release and firing rate induced by high doses of A412997 and L741742.

Simplified