Acute Administration of Leptin Produces Anxiolytic-like Effects: a Comparison with Fluoxetine

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2009 Oct 14

PMID 19823809

Citations 91

Authors

Jing Liu

Jacob C Garza

Jamaur Bronner

Chung Sub Kim

Wei Zhang

Xin-Yun Lu

Affiliations

Soon will be listed here.

Abstract

Rationale: Our previous studies in rats have shown that the adipocyte-derived hormone leptin induces antidepressant-like effects with a behavioral profile similar to selective serotonin reuptake inhibitor (SSRI) antidepressants. Acute SSRI treatment causes paradoxical anxiogenic responses, although chronic treatment has therapeutic effects on anxiety. However, the role of leptin in anxiety remains to be established.

Objectives: The scope of this study was to investigate the acute effects of leptin on anxiety-related behaviors in comparison with the SSRI antidepressant fluoxetine.

Materials And Methods: Adult male C57BL/6J mice received intraperitoneal injection of leptin or fluoxetine. Thirty minutes after injection, mice were subjected to the tail suspension test (TST) and forced swim test (FST) for evaluating antidepressant activity. Anxiety-like behavior was assessed in the elevated plus maze (EPM), social interaction, and open field tests 30 min following drug treatment.

Results: While leptin and fluoxetine showed similar antidepressant-like behavioral effects in the TST and FST, they differed in the behavioral assays for anxiety. Open arm exploration in the EPM was increased by leptin but decreased by fluoxetine. Analysis of social interaction revealed that distinct social behavioral components were modulated by leptin and fluoxetine. The total time of active social behaviors was increased by leptin but reduced by fluoxetine. In addition, self-grooming, a non-social behavior, was suppressed by leptin treatment. Neither leptin nor fluoxetine produced significant effects in the open field test.

Conclusions: In contrast to anxiogenic-like effects induced by acute fluoxetine, leptin elicits anxiolytic-like effects after acute administration. These results suggest that leptin has both antidepressant-like and anxiolytic-like properties.

Citing Articles

Neuropsychiatric Abnormalities in Metabolic Disturbances: Interplay of Adipokines and Neurotransmission.

Cheon S, Song J Mol Neurobiol. 2025; .

PMID: 40042730 DOI: 10.1007/s12035-025-04797-6.

Phytoconstituents of as a potential adjunct in the treatment of anxiety disorders: In vivo and in silico approaches.

Arobi Katha U, Begum Y, Mortuza M, Sharmin S, Rafiquzzaman M, Biswas S Heliyon. 2024; 10(23):e40728.

PMID: 39698094 PMC: 11652921. DOI: 10.1016/j.heliyon.2024.e40728.

Factors Associated with the Development of Depression and the Influence of Obesity on Depressive Disorders: A Narrative Review.

Alberti A, Coelho D, Vieira W, Moehlecke Iser B, Lampert R, Traebert E Biomedicines. 2024; 12(9).

PMID: 39335507 PMC: 11429137. DOI: 10.3390/biomedicines12091994.

The effect of SSRIs on unconditioned anxiety: a systematic review and meta-analysis of animal studies.

Heesbeen E, van Kampen T, Verdouw P, van Lissa C, Bijlsma E, Groenink L Psychopharmacology (Berl). 2024; 241(9):1731-1755.

PMID: 38980348 PMC: 11339141. DOI: 10.1007/s00213-024-06645-2.

Effect of acute and long-term exercise on leptin levels in depressed outpatients.

Heinen D, Heissel A, Heinzel S, Fydrich T, Strohle A, Rapp M BMC Public Health. 2023; 23(1):2509.

PMID: 38098007 PMC: 10722655. DOI: 10.1186/s12889-023-17362-4.

References

David D, Samuels B, Rainer Q, Wang J, Marsteller D, Mendez I . Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression. Neuron. 2009; 62(4):479-93. PMC: 2759281. DOI: 10.1016/j.neuron.2009.04.017. View

Atmaca M, Kuloglu M, Tezcan E, Ustundag B, Bayik Y . Serum leptin and cholesterol levels in patients with bipolar disorder. Neuropsychobiology. 2003; 46(4):176-9. DOI: 10.1159/000067809. View

Laposky A, Shelton J, Bass J, Dugovic C, Perrino N, Turek F . Altered sleep regulation in leptin-deficient mice. Am J Physiol Regul Integr Comp Physiol. 2005; 290(4):R894-903. DOI: 10.1152/ajpregu.00304.2005. View

Kurt M, Arik A, Celik S . The effects of sertraline and fluoxetine on anxiety in the elevated plus-maze test in mice. J Basic Clin Physiol Pharmacol. 2000; 11(2):173-80. DOI: 10.1515/jbcpp.2000.11.2.173. View

Simon P, Dupuis R, Costentin J . Thigmotaxis as an index of anxiety in mice. Influence of dopaminergic transmissions. Behav Brain Res. 1994; 61(1):59-64. DOI: 10.1016/0166-4328(94)90008-6. View

Berlant J . New drug development for post-traumatic stress disorder. Curr Opin Investig Drugs. 2003; 4(1):37-41. View

Xu L, Rensing N, Yang X, Zhang H, Thio L, Rothman S . Leptin inhibits 4-aminopyridine- and pentylenetetrazole-induced seizures and AMPAR-mediated synaptic transmission in rodents. J Clin Invest. 2007; 118(1):272-80. PMC: 2147669. DOI: 10.1172/JCI33009. View

Lister R . The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology (Berl). 1987; 92(2):180-5. DOI: 10.1007/BF00177912. View

Lucki I . The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behav Pharmacol. 1998; 8(6-7):523-32. DOI: 10.1097/00008877-199711000-00010. View

10.

Asakawa A, Inui A, Inui T, Katsuura G, A Fujino M, Kasuga M . Leptin treatment ameliorates anxiety in ob/ob obese mice. J Diabetes Complications. 2003; 17(2):105-7. DOI: 10.1016/s1056-8727(02)00185-x. View

11.

Spruijt B, van Hooff J, Gispen W . Ethology and neurobiology of grooming behavior. Physiol Rev. 1992; 72(3):825-52. DOI: 10.1152/physrev.1992.72.3.825. View

12.

Harvey J, Solovyova N, Irving A . Leptin and its role in hippocampal synaptic plasticity. Prog Lipid Res. 2006; 45(5):369-78. PMC: 1762032. DOI: 10.1016/j.plipres.2006.03.001. View

13.

Griebel G, Sanger D, Perrault G . The use of the rat elevated plus-maze to discriminate between non-selective and BZ-1 (omega 1) selective, benzodiazepine receptor ligands. Psychopharmacology (Berl). 1996; 124(3):245-54. DOI: 10.1007/BF02246664. View

14.

File S, Seth P . A review of 25 years of the social interaction test. Eur J Pharmacol. 2003; 463(1-3):35-53. DOI: 10.1016/s0014-2999(03)01273-1. View

15.

Lazosky A, Britton D . Effects of 5-HT-1A receptor agonists on CRF-induced behavior. Psychopharmacology (Berl). 1991; 104(1):132-6. DOI: 10.1007/BF02244567. View

16.

Hay-Schmidt A, Helboe L, Larsen P . Leptin receptor immunoreactivity is present in ascending serotonergic and catecholaminergic neurons of the rat. Neuroendocrinology. 2001; 73(4):215-26. DOI: 10.1159/000054638. View

17.

Griebel G, Blanchard D, Agnes R, Blanchard R . Differential modulation of antipredator defensive behavior in Swiss-Webster mice following acute or chronic administration of imipramine and fluoxetine. Psychopharmacology (Berl). 1995; 120(1):57-66. DOI: 10.1007/BF02246145. View

18.

Zarate Jr C, Singh J, Carlson P, Brutsche N, Ameli R, Luckenbaugh D . A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006; 63(8):856-64. DOI: 10.1001/archpsyc.63.8.856. View

19.

Calapai G, Corica F, Corsonello A, Sautebin L, Di Rosa M, Campo G . Leptin increases serotonin turnover by inhibition of brain nitric oxide synthesis. J Clin Invest. 1999; 104(7):975-82. PMC: 408549. DOI: 10.1172/JCI5867. View

20.

den Boer J, Westenberg H, de Leeuw A, van Vliet I . Biological dissection of anxiety disorders: the clinical role of selective serotonin reuptake inhibitors with particular reference to fluvoxamine. Int Clin Psychopharmacol. 1995; 9 Suppl 4:47-52. View