Chronic nandrolone decanoate exposure during adolescence affects emotional behavior and monoaminergic neurotransmission in adulthood.
Nandrolone decanoate, an anabolic androgen steroid (AAS) illicitly used by adult and adolescent athletes to enhance physical performance and body image, induces psychiatric side effects, such as aggression, depression as well as a spectrum of adverse physiological impairments. Since adolescence represents a neurodevelopmental window that is extremely sensitive to the detrimental effects of drug abuse, we investigated the long-term behavioral and neurophysiological consequences of nandrolone abuse during adolescence. Adolescent rats received daily injections of nandrolone decanoate (15 mg/kg, i.m.) for 14 days (PND 40-53). At early adulthood (PND 68), forced swim, sucrose preference, open field and elevated plus maze tests were performed to assess behavioral changes. In vivo electrophysiological recordings were carried out to monitor changes in electrical activity of serotonergic neurons of the dorsal raphe nucleus (DRN) and noradrenergic neurons of the locus coeruleus (LC). Our results show that after early exposure to nandrolone, rats display depression-related behavior, characterized by increased immobility in the forced swim test and reduced sucrose intake in the sucrose preference test. In addition, adult rats presented anxiety-like behavior characterized by decreased time and number of entries in the central zone of the open field and decreased time spent in the open arms of the elevated plus maze. Nandrolone decreased the firing rate of spontaneously active serotonergic neurons in the DRN while increasing the firing rate of noradrenergic neurons in the LC. These results provide evidence that nandrolone decanoate exposure during adolescence alters the emotional profile of animals in adulthood and significantly modifies both serotonergic and noradrenergic neurotransmission.
Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University and McGill University Health Center, Montreal, QC, Canada.
Quentin
Q
Rainer
Department of Theoretical and Applied Sciences, Biomedical Research Division, Neuroscience Center, University of Insubria, Busto Arsizio, VA, Italy.
Simona
S
Speziali
Department of Theoretical and Applied Sciences, Biomedical Research Division, Neuroscience Center, University of Insubria, Busto Arsizio, VA, Italy.
Tiziana
T
Rubino
Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University and McGill University Health Center, Montreal, QC, Canada.
Sergio
S
Dominguez-Lopez
Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University and McGill University Health Center, Montreal, QC, Canada.
Francis Rodriguez
FR
Bambico
Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University and McGill University Health Center, Montreal, QC, Canada. Electronic address: gabriella.gobbi@mcgill.ca.
Gabriella
G
Gobbi
Department of Theoretical and Applied Sciences, Biomedical Research Division, Neuroscience Center, University of Insubria, Busto Arsizio, VA, Italy. Electronic address: daniela.parolaro@uninsubria.it.
Daniela
D
Parolaro
D000200:Action Potentials / Q000187:drug effects; D059331:Adrenergic Neurons / Q000187:drug effects* / Q000502:physiology; D000367:Age Factors; D045930:Anabolic Agents / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000139:chemically induced*; D065847:Dorsal Raphe Nucleus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009277:Nandrolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D000077603:Nandrolone Decanoate; D051381:Rats; D017207:Rats, Sprague-Dawley; D059326:Serotonergic Neurons / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*
D045930:Anabolic Agents; D009277:Nandrolone; D000077603:Nandrolone Decanoate
Adolescence; Anxiety; Behavior; Depression; In vivo electrophysiology; Nandrolone decanoate; Noradrenaline; Serotonin