Leptin Prevents Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of Dopamine Receptors
Depression is a chronic and recurrent disorder, associated with high morbidity and risk of suicide. Leptin was firstly described as an anti-obesity hormone, but several actions of leptin in CNS have been reported. In fact, leptin regulates dopaminergic neurotransmission in mesolimbic areas and has a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fpsyt.2019.00125/full |
| _version_ | 1828486311968768000 |
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| author | Rafaela Carneiro Cordeiro Adriano José Maia Chaves Filho Nayana Soares Gomes Viviane de Sousa Tomaz Camila Dantas Medeiros Camila Dantas Medeiros Ana Isabelle de Góis Queiroz Michael Maes Danielle S. Macedo Andre F. Carvalho Andre F. Carvalho |
| author_facet | Rafaela Carneiro Cordeiro Adriano José Maia Chaves Filho Nayana Soares Gomes Viviane de Sousa Tomaz Camila Dantas Medeiros Camila Dantas Medeiros Ana Isabelle de Góis Queiroz Michael Maes Danielle S. Macedo Andre F. Carvalho Andre F. Carvalho |
| author_sort | Rafaela Carneiro Cordeiro |
| collection | DOAJ |
| description | Depression is a chronic and recurrent disorder, associated with high morbidity and risk of suicide. Leptin was firstly described as an anti-obesity hormone, but several actions of leptin in CNS have been reported. In fact, leptin regulates dopaminergic neurotransmission in mesolimbic areas and has antidepressant-like properties in stress-based models. In the present study, we investigated, for the first time, putative antidepressant-like effects of leptin in an animal model of depressive-like behaviors induced by lipopolysaccharide (LPS), and the potential involvement of dopamine receptors as mediators of those behavioral effects. Mice were injected leptin (1.5 mg/kg, IP) or imipramine prior to LPS administration. To evaluate the involvement of dopamine receptors, different experimental groups were pretreated with either the dopaminergic antagonist SCH23390, for D1 receptors or raclopride, for D2/D3 receptors, prior to leptin injection. Twenty-four hours post-LPS, mice were submitted to the forced swimming and sucrose preference tests. In addition, IL-1β levels were determined in the prefrontal cortex (PFC), hippocampus and striatum. BDNF levels were measured in the hippocampus. Our results showed that leptin, similarly to imipramine, prevented the core behavioral alterations induced by LPS (despair-like behavior and anhedonia), without altering locomotion. In neurochemical analysis, leptin restored LPS-induced changes in IL-1β levels in the PFC and striatum, and increased BDNF levels in the hippocampus. The blockade of dopamine D1 and D2/D3 receptors inhibited leptin's antidepressant-like effects, whilst only the blockade of D1-like receptors blunted leptin-induced increments in prefrontal IL-1β levels. Our results indicate that leptin has antidepressant-like effects in an inflammatory model of depression with the contribution, at least partial, of dopamine receptors. |
| first_indexed | 2024-12-11T09:29:31Z |
| format | Article |
| id | doaj.art-498a3be410334aad9b6d0ae95e47a15f |
| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-12-11T09:29:31Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj.art-498a3be410334aad9b6d0ae95e47a15f2022-12-22T01:13:02ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402019-03-011010.3389/fpsyt.2019.00125379129Leptin Prevents Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of Dopamine ReceptorsRafaela Carneiro Cordeiro0Adriano José Maia Chaves Filho1Nayana Soares Gomes2Viviane de Sousa Tomaz3Camila Dantas Medeiros4Camila Dantas Medeiros5Ana Isabelle de Góis Queiroz6Michael Maes7Danielle S. Macedo8Andre F. Carvalho9Andre F. Carvalho10Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Universidade Federal do CearáFortaleza, BrazilNeuropharmacology Laboratory, Department of Physiology and Pharmacology, Universidade Federal do CearáFortaleza, BrazilNeuropharmacology Laboratory, Department of Physiology and Pharmacology, Universidade Federal do CearáFortaleza, BrazilNeuropharmacology Laboratory, Department of Physiology and Pharmacology, Universidade Federal do CearáFortaleza, BrazilNeuropharmacology Laboratory, Department of Physiology and Pharmacology, Universidade Federal do CearáFortaleza, BrazilMcGill Group for Suicide Studies, Douglas Mental Health Institute, McGill UniversityMontreal, QC, CanadaNeuropharmacology Laboratory, Department of Physiology and Pharmacology, Universidade Federal do CearáFortaleza, BrazilDepartment of Psychiatry, Faculty of Medicine, Chulalongkorn UniversityBangkok, ThailandNeuropharmacology Laboratory, Department of Physiology and Pharmacology, Universidade Federal do CearáFortaleza, BrazilDepartment of Psychiatry, University of TorontoToronto, ON, CanadaCentre for Addiction and Mental HealthToronto, ON, CanadaDepression is a chronic and recurrent disorder, associated with high morbidity and risk of suicide. Leptin was firstly described as an anti-obesity hormone, but several actions of leptin in CNS have been reported. In fact, leptin regulates dopaminergic neurotransmission in mesolimbic areas and has antidepressant-like properties in stress-based models. In the present study, we investigated, for the first time, putative antidepressant-like effects of leptin in an animal model of depressive-like behaviors induced by lipopolysaccharide (LPS), and the potential involvement of dopamine receptors as mediators of those behavioral effects. Mice were injected leptin (1.5 mg/kg, IP) or imipramine prior to LPS administration. To evaluate the involvement of dopamine receptors, different experimental groups were pretreated with either the dopaminergic antagonist SCH23390, for D1 receptors or raclopride, for D2/D3 receptors, prior to leptin injection. Twenty-four hours post-LPS, mice were submitted to the forced swimming and sucrose preference tests. In addition, IL-1β levels were determined in the prefrontal cortex (PFC), hippocampus and striatum. BDNF levels were measured in the hippocampus. Our results showed that leptin, similarly to imipramine, prevented the core behavioral alterations induced by LPS (despair-like behavior and anhedonia), without altering locomotion. In neurochemical analysis, leptin restored LPS-induced changes in IL-1β levels in the PFC and striatum, and increased BDNF levels in the hippocampus. The blockade of dopamine D1 and D2/D3 receptors inhibited leptin's antidepressant-like effects, whilst only the blockade of D1-like receptors blunted leptin-induced increments in prefrontal IL-1β levels. Our results indicate that leptin has antidepressant-like effects in an inflammatory model of depression with the contribution, at least partial, of dopamine receptors.https://www.frontiersin.org/article/10.3389/fpsyt.2019.00125/fullleptindepressionLPSdopamineprefrontal cortexpsychiatry |
| spellingShingle | Rafaela Carneiro Cordeiro Adriano José Maia Chaves Filho Nayana Soares Gomes Viviane de Sousa Tomaz Camila Dantas Medeiros Camila Dantas Medeiros Ana Isabelle de Góis Queiroz Michael Maes Danielle S. Macedo Andre F. Carvalho Andre F. Carvalho Leptin Prevents Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of Dopamine Receptors Frontiers in Psychiatry leptin depression LPS dopamine prefrontal cortex psychiatry |
| title | Leptin Prevents Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of Dopamine Receptors |
| title_full | Leptin Prevents Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of Dopamine Receptors |
| title_fullStr | Leptin Prevents Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of Dopamine Receptors |
| title_full_unstemmed | Leptin Prevents Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of Dopamine Receptors |
| title_short | Leptin Prevents Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of Dopamine Receptors |
| title_sort | leptin prevents lipopolysaccharide induced depressive like behaviors in mice involvement of dopamine receptors |
| topic | leptin depression LPS dopamine prefrontal cortex psychiatry |
| url | https://www.frontiersin.org/article/10.3389/fpsyt.2019.00125/full |
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