Acute administration of leptin produces anxiolytic-like effects: a comparison with fluoxetine

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.

Central administration of ghrelin alters emotional responses in rats: behavioural, electrophysiological and molecular evidence

“…However even though the data concerning the relationship between ghrelin and psychiatric disorders appears conflicting, taken together, these studies in humans and rodents suggest that both short and long term stimulation of the central ghrelin signalling system is likely to be involved in the regulation of mood. This appears in line with the evidence that several peptides involved in the regulation of appetite and metabolism such as the neuropetide Y and the cholecystokinin as well as other hormones like leptin played also a key role in the regulation of emotional process (Lu et al, 2006, Lu, 2007, Liu et al, 2010, Rotzinger et al, 2010.…”

Hippocampal Leptin Signaling Reduces Food Intake and Modulates Food-Related Memory Processing

“…Runway speed measured after leaving the starting point, however, was not influenced by leptin administration, suggesting that VHPC leptin did not influence locomotor function. If exogenous leptin decreased anxiety levels, which has previously been shown in rodents following peripheral leptin delivery (Liu et al, 2010), then the reduced anxiety would be more likely to decrease the latency to start, which differs from the observed increase in latency in the present results. Furthermore, if general changes in appetitive motivation were responsible for the observed leptin-induced increase in latency to leave the starting position, it is unclear how this type of performance decrement could specifically influence latency on early trials, without also altering latency on later trials throughout the 10-trial runway session.…”

Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity

“…Behavioral tests, including sucrose preference, learned helplessness, hot plate, tail suspension test, forced swim test, locomotor activity, visual cliff, and olfactory function, were performed as described previously (58)(59)(60). For experimental details, see SI Materials and Methods.…”