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

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.

Fedotova J ，Soultanov V ，Nikitina T ，Roschin V ，Ordyan N ，Hritcu L ... -  《-》

Antidepressant-Like Effect of Ropren® in β-Amyloid-(25-35) Rat Model of Alzheimer's Disease with Altered Levels of Androgens.

Soultanov V ，Fedotova J ，Nikitina T ，Roschin V ，Ordyan N ，Hritcu L ... -  《-》

Cognitive-enhancing activities of the polyprenol preparation Ropren® in gonadectomized β-amyloid (25-35) rat model of Alzheimer's disease.

The present preclinical study was designed to examine the effects of prolonged Ropren® administration (8.6 mg/kg, orally, once daily, 28 days) in a β-amyloid (25-35) rat model of Alzheimer's disease following gonadectomy. The experimental model was created by intracerebroventricular injection of β-amyloid (25-35) into gonadectomized (GDX) rats and GDX rats with testosterone propionate (TP, 0.5mg/kg, subcutaneous, once daily, 28 days) supplementation. Ropren® was administered to the GDX rats and GDX rats treated with TP. Memory performance was assessed using the passive avoidance and the Morris water maze tests and the spontaneous locomotor activity was assessed using the open field test. Treatment with Ropren® significantly improved and restored the cognitive ability of GDX rats with β-amyloid (25-35)-induced amnesia in the passive avoidance test and Morris water maze. Co-administration of Ropren® with TP exerted a markedly synergistic memory-enhancing effect in the GDX rats with β-amyloid (25-35)-induced amnesia on the same models of memory testing. Ropren® administered alone or together with TP significantly enhanced crossing, frequency of rearing and grooming of the GDX rats with β-amyloid (25-35)-induced amnesia in the open field test. These results indicate that Ropren® has a marked memory-enhancing action in the experimental model of Alzheimer's disease in male rats with altered levels of androgens.

Fedotova J ，Soultanov V ，Nikitina T ，Roschin V ，Ordyan N ，Hritcu L ... -  《-》

[Effect of new polyprenol drug ropren on anxiety-depressive-like behavior in rats with experimental Alzheimer disease].

Fedotova IuO ，Sultanov VS ，Kuznetsova NN ，Roshchin VI ，Nikitina TV ... -  《-》

Testosterone promotes anxiolytic-like behavior in gonadectomized male rats via blockade of the 5-HT(1A) receptors.

This study was designed to examine an anxiety-like behavior in the adult gonadectomized (GDX) male rats subjected to testosterone propionate (TP) treatment alone or in combination with 8-OH-DPAT, a 5-HT1A receptor agonist, or with NAN-190, 5-HT1A receptor antagonist. Two weeks after gonadectomy, GDX rats were subjected by treatments with the solvent, TP (0.5mg/kg, s.c.), 8-OH-DPAT (0.05mg/kg, s.c.), NAN-190 (0.1mg/kg, i.p.), TP in combination with 8-OH-DPAT or NAN-190 during 14days. Anxiety behavior was assessed in the elevated plus maze (EPM) and the open field test (OFT). 8-OH-DPAT treatment failed to modify the anxiety-like behavior of GDX rats in the EPM as compared to the GDX rats given with oil solvent. NAN-190 injected alone or in combination with TP to GDX rats resulted in a significant anxiolytic-like effect as compared to the GDX given with oil solvent or TP application. Our data indicate that the combination of NAN-190 and TP is more effective than TP alone in GDX rats inducing a more profound anxiolytic-like effect in the EPM. Thus, the results of this study suggest that effects of 5-HT1A receptor agonist/antagonist can modify anxiety level in opposite direction in male rats after gonadectomy.

Fedotova J ，Hritcu L 《-》