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.
Laboratory of Neuroendocrinology, I.P. Pavlov Institute of Physiology of the Russian Academy of Sciences, 6 Emb. Makarova, St. Petersburg 199034, Russia; Laboratory of Comparative Somnology and Neuroendocrinology, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 44 Tores pr., St. Petersburg 194223, Russia; International Research Centre «Biotechnologies of the Third Millennium», ITMO University, 9 Lomonosova str., St. Petersburg 191002, Russia. Electronic address: julia.fedotova@mail.ru.
Julia
J
Fedotova
Solagran Limited, Biotechnology Company, 98-106, Moray St, South Melbourne, 3205, Australia.
Vagif
V
Soultanov
Laboratory of Functional Biochemistry of Invertebrates, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, pr. Torez 44, St. Petersburg 194223, Russia.
Tamara
T
Nikitina
Department of Wood Chemistry, State Forest Technical Academy, 5 Institutsky per., St. Petersburg 194021, Russia.
Victor
V
Roschin
Laboratory of Comparative Somnology and Neuroendocrinology, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 44 Tores pr., St. Petersburg 194223, Russia.
Natalia
N
Ordyan
Department of Biology, Alexandru Ioan Cuza University of Iasi, Bd. Carol I, No. 11, 700506, Romania. Electronic address: hritcu@uaic.ro.
Lucian
L
Hritcu
D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D015306:Biogenic Monoamines / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009919:Orchiectomy / Q000009:adverse effects; D010446:Peptide Fragments / Q000633:toxicity; D028222:Picea; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D016229:Amyloid beta-Peptides; D015306:Biogenic Monoamines; D010446:Peptide Fragments; D010936:Plant Extracts; C074636:amyloid beta-protein (25-35)
Alzheimer’s disease; Anxiety; Monoamines; Ropren(®); Testosterone