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, Robert L. Meisel, Paul G. Mermelstein

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6 Scopus citations


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, 1.5 mg) or vehicle (oil) in three experimental groups: intact-oil, GDX-oil and GDX-DHT. Spine density and morphology, measured 24 hours 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.

Original languageEnglish (US)
Article numbere12918
JournalJournal of Neuroendocrinology
Issue number1
StatePublished - Dec 19 2020

Bibliographical note

Funding Information:
Financial support was received from NIH DA041808 to PGM and from Norwegian Research Council grant #251320 to EMS. PTH was supported by a Personal Overseas Research Grant from the Norwegian Research Council. We thank Anna Peyla for technical assistance with immunohistochemistry.

Publisher Copyright:
© 2020 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology


  • androgen
  • gonadectomy
  • pCREB
  • plasticity
  • spine density


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