Citation

Cordeiro RC, Chaves Filho AJM, Gomes NS, De Sousa Tomaz V, Medeiros CD, De Góis Queiroz AI, Maes M, Macedo DS, Carvalho AF. Front. Psychiatry 2019; 10(MAR).

Copyright

(Copyright © 2019, Frontiers Media)

DOI

10.3389/fpsyt.2019.00125

PMID

unavailable

Abstract

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. Copyright © 2019 Cordeiro, Chaves Filho, Gomes, Tomaz, Medeiros, Queiroz, Maes, Macedo and Carvalho.

Language: en

Keywords

Depression; male; Psychiatry; Prefrontal cortex; depression; prefrontal cortex; hippocampus; Dopamine; controlled study; imipramine; drug mechanism; nonhuman; dopamine receptor; mouse; brain level; animal experiment; leptin; animal model; anhedonia; dopamine 2 receptor; Article; animal tissue; protein function; interleukin 1beta; brain derived neurotrophic factor; corpus striatum; Leptin; 8 chloro 2,3,4,5 tetrahydro 3 methyl 5 phenyl 1h 3 benzazepin 7 ol hydrogen maleate; dopamine 1 receptor; Swiss Webster mouse; open field test; locomotion; antidepressant activity; clinical outcome; forced swim test; sucrose preference test; immobility time; dopamine 3 receptor; lipopolysaccharide; LPS; raclopride