Effects of gonadectomy and dihydrotestosterone on neuronal plasticity in motivation and reward related brain regions in the male rat.

Patty T Huijgens,Eelke M S Snoeren,Paul G Mermelstein,Robert L Meisel

doi:10.1111/jne.12918

Abstract

Gonadal hormones affect neuronal morphology to ultimately regulate behaviour. In female rats, oestradiol mediates spine plasticity in hypothalamic and limbic brain structures, contributing to long-lasting effects on motivated behaviour. Parallel effects of androgens in male rats have not been extensively studied. Here, we investigated the effect of both castration and androgen replacement on spine plasticity in the nucleus accumbens shell and core (NAcSh and NAcC), caudate putamen (CPu), medial amygdala (MeA) and medial preoptic nucleus (MPN). Intact and castrated (gonadectomy [GDX]) male rats were treated with dihydrotestosterone (DHT, 1.5mg) or vehicle (oil) in three experimental groups: intact-oil, GDX-oil and GDX-DHT. Spine density and morphology, measured 24hours after injection, were determined through three-dimensional reconstruction of confocal z-stacks of DiI-labelled dendritic segments. We found that GDX decreased spine density in the MPN, which was rescued by DHT treatment. DHT also increased spine density in the MeA in GDX animals compared to intact oil-treated animals. By contrast, DHT decreased spine density in the NAcSh compared to GDX males. No effect on spine density was observed in the NAcC or CPu. Spine length and spine head diameter were unaffected by GDX and DHT in the investigated brain regions. In addition, immunohistochemistry revealed that DHT treatment of GDX animals rapidly increased the number of cell bodies in the NAcSh positive for phosphorylated cAMP response-element binding protein, a downstream messenger of the androgen receptor. These findings indicate that androgen signalling plays a role in the regulation of spine plasticity within neurocircuits involved in motivated behaviours.

Highlights

Gonadal hormones are key regulators of rewarding behavior (Paredes, 2010; Tonn Eisinger et al, 2018b)
3.1 Dendritic spine plasticity To study the effects of both GDX and androgen replacement on dendritic spine plasticity, we compared intact males treated with oil to GDX males treated with oil, to GDX males treated with DHT
We found that GDX affected spine plasticity in the medial preoptic nucleus (MPN) (Figure 2A, [F(2,15)=10.70, p=0.0013, η2 = 0.59]) by decreasing spine density [mean diff. vs. intact = 2.03, p=0.0037, g = 2.35]

Summary

Introduction

Gonadal hormones are key regulators of rewarding behavior (Paredes, 2010; Tonn Eisinger et al, 2018b). Previous research has shown that spine density, spine morphology, and dendrite length can be impacted by gonadal hormones in multiple brain regions involved in motivation (Calizo and Flanagan-Cato, 2002; Cooke and Woolley, 2005; Cunningham et al, 2007; Peterson et al, 2015) These hormone-induced structural reorganizations are both sexually dimorphic and strikingly different between brain regions, and have been linked to motivated behavior, learning, memory, and addiction (Frankfurt and Luine, 2015; McEwen and Milner, 2017; Tobiansky et al, 2018; Tonn Eisinger et al, 2018a)

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