The role of neuropeptide-Y in nandrolone decanoate-induced attenuation of antidepressant effect of exercise

Abstract

Since the increased prevalence of anabolic androgenic steroids abuse in last few decades is usually accompanied by various exercise protocols, the scope of our study was to evaluate the effects of chronic nandrolone decanoate administration in supraphysiological dose and a prolonged swimming protocol (alone and simultaneously with nandrolone decanoate) on depressive state in male rats. Simultaneously, we investigated the possible alterations in neuropeptide Y (NPY) content in blood and the hippocampus, in order to determine the role of NPY in the modulation of depressive-like behavior.Exercise induced antidepressant effects in tail suspension test (decrease of the total duration of immobility), as well as significant increase in the number of hippocampal NPY-interneurons in CA1 region. Chronic nandrolone decanoate treatment attenuated the beneficial antidepressant effects of exercise as measured by the tail suspension test parameters. Simultaneously, nandrolone decanoate treatment resulted in diminution of NPY content both in blood (decreased serum levels) and in hippocampus (the significant decrease in NPY expression in all three investigated hippocampal regions—CA1, CA2/3 and DG). Our findings indicate that alterations in serum and hippocampal NPY contents may underlie the changes in depressive state in rats. The exercise was beneficial as it exerted antidepressant effect, while chronic nandrolone decanoate treatment resulted in depressive-like behavior. Furthermore, the behavioral indicators of depression showed strong correlations with the serum levels and the hippocampal content of NPY.

The opposite effects of nandrolone decanoate and exercise on anxiety levels in rats may involve alterations in hippocampal parvalbumin–positive interneurons

“…Following decapitation, rat brains (after immediate removal from the skull) proceeded previously described procedure [ 23 ]—fixation in 4% neutral buffered formaldehyde, dehydration and were embedded. 5 μm thick coronal brain sections were dewaxed, rehydrated and treated with citrate buffer (pH 6.0) in the microwave for antigen retrieval.…”

“…Since hippocampus plays one of the key roles in mood modulation and may be involved in control of some specific behavioral patterns [ 23 ], alterations in hippocampal PV content have been proposed as a possible explanation for exercise-induced behavioral changes. It has been reported that behavioral alterations induced by various types of exercise protocols were accompanied with specific modification in hippocampal parvalbumin expression [ 24 – 26 ].…”

The Impact of Hippocampal Sex Hormones Receptors in Modulation of Depressive-Like Behavior Following Chronic Anabolic Androgenic Steroids and Exercise Protocols in Rats

“…The ND groups (ND and E+ND) and TE groups (TE and E+TE) received 20 mg/kg subcutaneous injections of AASs (DEKA 300, SteroxLab, EU and Testosteron depo, Galenika a.d., Serbia, respectively) weekly, in a single dose, for 6 weeks. The final doses of ND and TE were chosen to mimic the doses for heavy human AASs abusers (Kanayama et al, 2008), since these were confirmed to be sufficient to induce behavioral alterations in our previous studies (Selakovic et al, 2016, 2017; Joksimović et al, 2017a,b). The exercise protocols also lasted for 6 weeks (in groups E, E+ND, and E+TE).…”

“…This test is based on the assumption that an animal will actively try to escape an aversive (stressful) stimulus (Chermat et al, 1986). The test was performed according to a previously described procedure (Joksimović et al, 2017b). The whole test trial was recorded using a video camera, and recordings were analyzed in order to determine the following parameters (data presented in Supplementary Table S1): the latency to the first immobility, the number of immobility episodes, the total duration of immobility (TDI) and the average duration of an immobility episode (the ratio of the TDI to the number of immobility episodes).…”

“…Although it was observed that acute exercise of any intensity significantly improved depressive symptoms in women (Meyer et al, 2016), other sources have shown that correlations between physical activity and depression depend on the intensity of the exercise (Noh et al, 2015). After all, the results of study showing the most beneficial behavioral effects of exercise, including antidepressant effects, were achieved by using prolonged exercise protocols with mild (erobic) intensity (Joksimović et al, 2017b).…”