Ropren® treatment reverses anxiety-like behavior and monoamines levels in gonadectomized rat model of Alzheimer's disease

Biomed Pharmacother. 2016 Oct:83:1444-1455. doi: 10.1016/j.biopha.2016.08.065. Epub 2016 Sep 6.

Abstract

Previous studies indicated that reduced androgen levels may contribute to both physical and cognitive disorders in men, including Alzheimer's disease. New drug candidates for Alzheimer's disease in patients with androgen deficiency should ideally be able to act not only on multiple brain targets but also to correct impaired endocrine functions in hypogonadal men with Alzheimer's disease. Ropren® is one such candidate for the treatment of Alzheimer's disease in men with an imbalance of androgens. Accordingly, the aim of the current study was to examine the effects of long-term Ropren® administration (8.6mg/kg, orally, once daily, for 28 days) on the anxiety-like behavior and monoamines levels in the rat hippocampus using a β-amyloid (25-35) rat model of Alzheimer's disease following gonadectomy. Ropren® was administered to the gonadectomized (GDX) rats and GDX rats treated with testosterone propionate (TP, 0.5mg/kg, subcutaneous, once daily, for 28 days). Anxiety-like behavior was assessed in the elevated plus maze (EPM) and the light-dark test (LDT), locomotor and grooming activities were assessed in the open field test (OFT). Ropren® alone or in combination with TP-induced anxiolytic effects as evidenced in the EPM and in the LDT and increased locomotor activity in the OFT. Additionally, it was observed that dopamine (DA) and serotonin (5-HT) levels increased while 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio in the hippocampus decreased. Our results indicate that Ropren® has a marked anxiolytic-like action due to an increase in the monoamines levels in the experimental rat model of Alzheimer's disease with altered levels of androgens.

Keywords: Alzheimer’s disease; Anxiety; Monoamines; Ropren(®); Testosterone.

MeSH terms

  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Anxiety / chemically induced
  • Anxiety / drug therapy*
  • Anxiety / metabolism*
  • Biogenic Monoamines / metabolism*
  • Disease Models, Animal*
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Orchiectomy / adverse effects
  • Peptide Fragments / toxicity
  • Picea
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Rats
  • Rats, Wistar
  • Treatment Outcome

Substances

  • Amyloid beta-Peptides
  • Biogenic Monoamines
  • Peptide Fragments
  • Plant Extracts
  • amyloid beta-protein (25-35)