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• W3083482223 endingPage "104844" @default.
• W3083482223 startingPage "104844" @default.
• W3083482223 abstract "Although multiple studies report that unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc) in rats induce depressive-like behaviors and hyperactivity of the lateral habenula (LHb), effects of dopamine (DA) D 4 receptors in the LHb on depressive-like behaviors are unclear. Here we found that intra-LHb injection of the different doses of D 4 receptor agonist A412997 and antagonist L741742 produced the different behavioral responses in SNc sham-lesioned rats, and only the high doses of A412997 and L741742 increased the expression of depressive-like behaviors or produced antidepressant-like effects in SNc-lesioned rats. The low doses of A412997 and L741742 altered the firing rate of LHb neurons and release of DA, GABA and glutamate in the LHb via the GABAergic rostromedial tegmental nucleus (RMTg) in SNc sham-lesioned rats, but not in SNc-lesioned rats. The high doses of A412997 and L741742 also altered the firing rate and release of the transmitters in both SNc sham-lesioned and SNc-lesioned rats, whereas these effects were not involved in the RMTg. Lesions of the SNc shortened the duration of significant effects on the firing rate and release of the transmitters induced by the high doses of A412997 and L741742. These findings suggest that D 4 receptors in the LHb are involved in depression-like behaviors via the pre- and post-synaptic mechanisms and depletion of DA decreases the function and/or the expression of both pre- and post-synaptic D 4 receptors. This study also points to the importance of the pre-synaptic D 4 receptors in the regulation of Parkinson's disease-related depression. • Activation and blockade of LHb D 4 Rs regulate depressive-like behaviors. • The behavioral responses are related to the doses of the D 4 R agonist and antagonist. • The low doses alter LHb neuron activity and the transmitter release via the RMTg. • The changes induced by the high doses are not involved in the RMTg. • The pre-synaptic D 4 Rs play an important role in regulating PD-related depression." @default.
• W3083482223 created "2020-09-11" @default.
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• W3083482223 date "2020-11-01" @default.
• W3083482223 modified "2023-09-24" @default.
• W3083482223 title "Dopamine D4 receptors in the lateral habenula regulate depression-related behaviors via a pre-synaptic mechanism in experimental Parkinson's disease" @default.
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• W3083482223 doi "https://doi.org/10.1016/j.neuint.2020.104844" @default.
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