Ghrelin, a Potential Antidepressant in Adult Rats, does not Reduce Depressive‐like Symptoms in Juvenile Rats
Authors: Jackson Thomas Michael , Stanley Erica M. , Ostrowski Tim D. , Middlemas David S. 
Published: June 2021

Background

Depression is a chronic psychiatric disorder that affects children and adolescents across the globe. There is an unmet need for better treatment options for juvenile patients. The brain‐gut peptide hormone ghrelin has been shown to reduce depressive‐like behavior and increase hippocampal neurogenesis in adult rodent models. However, there have been no studies to support this same role for ghrelin in behavior or neurogenesis in juvenile rats.

Methods

Ghrelin was dissolved in artificial cerebrospinal fluid (aCSF, vehicle) and injected via intracerebroventricular (icv) injection, using stereotaxic coordinates, in juvenile Sprague‐Dawley rats (PND 22, 51±1.3 g). To evaluate a dose‐response relationship and determine the most effective concentration of ghrelin (0.2, 0.5, or 1 nM), a Feeding Behavior Assay was used. Behavioral tests to measure peptide effects on depression included the Forced Swim Test (FST) and the Tail Suspension Test (TST). Hippocampal mitogenesis [mitotic cell division] and neurogenesis were quantified using immunohistochemistry: mitogenesis was visualized using the exogenous cell tracer BrdU, and neurogenesis was visualized using both BrdU and the endogenous neuronal marker NeuN.

Results

Rats treated with 0.5 nM ghrelin, compared to the other concentrations tested, consumed the greatest amount of food; therefore, the 0.5 nM concentration of ghrelin was used in all subsequent experiments. The TST showed that the ghrelin treated rats spent more time immobile than the control rats (p=0.043, n=8/group), indicating a greater degree of depressive‐like behavior. On the other hand, the FST showed no difference in behavior between the groups. Furthermore, there was a larger inter‐individual variability in the FST than in the TST (p=0.007, n=8/group). Preliminary mitogenesis and neurogenesis experiments did not yield a difference between ghrelin and vehicle groups.

Conclusions

Feeding behavior results indicated that 0.5 nM ghrelin produced the most potent peptide effect. The FST did not yield a difference between treatment and control groups. The TST was shown to work for juvenile rats, and it showed that ghrelin increases immobility time, compared to the vehicle group. Tests to measure depressive‐like behavior showed a significant increase in immobility time in the ghrelin treated group. These results suggest that ghrelin induces depressive‐like behavior in juvenile rats, which is in contrast with results obtained from adult rat studies, where ghrelin reduced depressive‐like behavior. This study further highlights the urgent need to better understand depression in juveniles, so that more effective treatment options are explored and developed. We are currently testing whether ghrelin treatment increases the rates of mitogenesis and neurogenesis to identify changes in brain regions implicated in the etiology of depression.

Support or Funding Information

Funded by the A.T. Still University of Health Sciences ‐ Kirksville College of Osteopathic Medicine Graduate Program Committee

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.