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Satellite cells (SCs) are mononuclear myogenic stem cells located between the basal lamina and plasmalemma of the skeletal muscle fiber. They are responsible for postnatal skeletal muscle growth, repair and regeneration. Once activated, SCs divide and fuse to the muscle fibers where their nuclei become new myonuclei. Earlier studies suggested that SCs were either randomly or evenly distributed along muscle fibers. However, myonuclei were found to be more concentrated at tapered ends of muscle fibers. Myogenic regulatory factors, mainly MyoD and Myogenin, are expressed by active SCs. Previous in vitro and prenatal studies suggested that MyoD expression demarcates the end of proliferation while Myogenin can demarcate the differentiation stage within myoblasts. Few in vivo studies have reported the expression of MyoD and Myogenin within SCs, and none have attempted to discern their expression patterns during growth. Meat producing chickens represent a unique model for natural hypertrophy within muscle fibers. However, very little is known about the distribution of SCs within these naturally hypertrophied fibers, and whether this distribution is comparable to that of experimental models of hypertrophy. Nandrolone Decanoate is the anabolic steroid most commonly used to increase skeletal muscle mass and strength, although little is known of its effects on SCs. This thesis expands our understanding of SCs by examining the following hypotheses: 1) there is a greater frequency (number of SC nuclei over all nuclei within the basal laminae) and a higher concentration (less surface area of sarcolemma per SC) of SCs at the ends of developing skeletal muscle fibers, 2) MyoD and Myogenin transcription myogenic factors have distinctive patterns of expression within SC nuclei during maturation, 3) there are greater frequency and concentration of SCs and greater number of myonuclei in naturally hypertrophied muscle fibers compared to their control, and 4) there is a greater frequency and a greater concentration of SCs in Nandrolone treated birds than in controls. Chicken pectoralis muscle was the main experimental model used in this thesis because of its overlapping fibers arranged in series, the presence of neonatal myosin at the fiber ends and relative homogeneity of fiber type. Immunocytochemical techniques that include an antibody against Pax7 to identify SC nuclei were applied, and computer image analyses were then used to quantify the numbers of SC nuclei and myonuclei within muscle fibers. This thesis demonstrates that throughout development there is a greater frequency and concentration of SCs at the ends of developing skeletal muscle fibers, which indicates a major contribution of these cells in the longitudinal growth of muscle fibers. It also reveals that MyoD and Myogenin each has a distinctive pattern of expression within SCs during in vivo postnatal development. The expression of MyoD increases significantly during maturation, while Myogenin expression remains steady. This finding suggests that each of these myogenic factors play a different role in the postnatal activation of SCs. Lastly, it is the first study to show a greater frequency and a higher concentration of SCs within both naturally and Nandrolone induced hypertrophied muscle fibers. This indicates SCs may be critically involved during postnatal skeletal muscle growth and hypertrophy.

Satellite cells (SCs) are mononuclear myogenic stem cells located between the basal lamina and plasmalemma of the skeletal muscle fiber. They are responsible for postnatal skeletal muscle growth, repair and regeneration. Once activated, SCs divide and fuse to the muscle fibers where their nuclei become new myonuclei. Earlier studies suggested that SCs were either randomly or evenly distributed along muscle fibers. However, myonuclei were found to be more concentrated at tapered ends of muscle fibers. Myogenic regulatory factors, mainly MyoD and Myogenin, are expressed by active SCs. Previous in vitro and prenatal studies suggested that MyoD expression demarcates the end of proliferation while Myogenin can demarcate the differentiation stage within myoblasts. Few in vivo studies have reported the expression of MyoD and Myogenin within SCs, and none have attempted to discern their expression patterns during growth. Meat producing chickens represent a unique model for natural hypertrophy within muscle fibers. However, very little is known about the distribution of SCs within these naturally hypertrophied fibers, and whether this distribution is comparable to that of experimental models of hypertrophy. Nandrolone Decanoate is the anabolic steroid most commonly used to increase skeletal muscle mass and strength, although little is known of its effects on SCs. This thesis expands our understanding of SCs by examining the following hypotheses: 1) there is a greater frequency (number of SC nuclei over all nuclei within the basal laminae) and a higher concentration (less surface area of sarcolemma per SC) of SCs at the ends of developing skeletal muscle fibers, 2) MyoD and Myogenin transcription myogenic factors have distinctive patterns of expression within SC nuclei during maturation, 3) there are greater frequency and concentration of SCs and greater number of myonuclei in naturally hypertrophied muscle fibers compared to their control, and 4) there is a greater frequency and a greater concentration of SCs in Nandrolone treated birds than in controls. Chicken pectoralis muscle was the main experimental model used in this thesis because of its overlapping fibers arranged in series, the presence of neonatal myosin at the fiber ends and relative homogeneity of fiber type. Immunocytochemical techniques that include an antibody against Pax7 to identify SC nuclei were applied, and computer image analyses were then used to quantify the numbers of SC nuclei and myonuclei within muscle fibers. This thesis demonstrates that throughout development there is a greater frequency and concentration of SCs at the ends of developing skeletal muscle fibers, which indicates a major contribution of these cells in the longitudinal growth of muscle fibers. It also reveals that MyoD and Myogenin each has a distinctive pattern of expression within SCs during in vivo postnatal development. The expression of MyoD increases significantly during maturation, while Myogenin expression remains steady. This finding suggests that each of these myogenic factors play a different role in the postnatal activation of SCs. Lastly, it is the first study to show a greater frequency and a higher concentration of SCs within both naturally and Nandrolone induced hypertrophied muscle fibers. This indicates SCs may be critically involved during postnatal skeletal muscle growth and hypertrophy.

Reproduction de : Thèse de doctorat : Chimie : Lyon 1 : 2008. / Titre provenant de l'écran titre. Bibliogr. en fin de parties.

Altas doses de esteróides anabólicos androgênicos (EAA) são utilizadas, sem indicação terapêutica, por indivíduos que visam aumentara força muscular ou melhorar a aparência física. Entretanto, os efeitos benéficos destas substâncias sobre o desempenho atlético são questionáveis, e sabe-se que esta prática é acompanhada de muitos efeitos colaterais. Este estudo teve por objetivo analisar as alterações histológicas e morfométricas das fibras do músculo sóleo e melhora no desempenho de ratos submetidos a um programa de treinamento físico, associado ou não à administração do esteróide anabólito decanoato de nandrolona. Os animais foram divididos em quatro grupos: sedentário + veículo (SC); treinado + veículo (TC); sedentário + EAA (SE); treinado + EAA (TE). Os animais foram tratados, por 4 semanas, com veículo (propilenoglicol, 0,2 mL/Kg) ou decanoato de nandrolona (Deca-Durabolin, 5 mg/Kg), i.m., 1 x/semana. O treinamento físico foi realizado através de saltos em meio líquido (4 séries, 10 repetições, 60 segundos de intervalo entre as séries), 50-80% do peso corporal, 3 dias/semana, 4 semanas. Antes e após o treinamento os animais foram submetidos a um teste de fadiga. Após o sacrifício, o músculo sóleo direito foi retirado. Cortes do terço médio desse músculo foram feitos em micrótomo criostato e corados pela técnica HE. Os animais submetidos ao treinamento físico (TC) e (TE) apresentaram fibras musculares com maior área, quando comparados com os animais controle (SC e SE). Não foram observadas diferenças no desempenho entre os grupos. Os resultados sugerem que o treinamento físico produz hipertrofia de forma semelhante, tanto no grupo que recebeu EAA quanto no que recebeu óleo mineral. No entanto, o grupo TE apresentou sinais de maior degeneração. / High doses of anabolic androgenic steroids (AAS) are used without therapeutic indication in order to increase the muscle power or improve the physical appearance. However the beneficial effects of AAS on the athletic performance are still questionable and it is well established that AAS abuse is associated with many detrimental side-effects. The objective of this study was to analyze the histological and morphometrical alterations of the fibers from the soleum muscle and performance improvement of rats submitted to a physical training, associated not to the administration of the anabolic steroid decanoate of nandrolone. Male Wistar rats were divided into four groups: sedentary + vehicle (SC), trained + vehicle (TC), sedentary + AAS (SE) and trained + AAS (TE). The animals were treated for 4 weeks with vehicle (propyleneglycol, 0.2 mL/Kg) or nandrolone decanoate (Deca-Durabolin, 5 mg/Kg), i.m., 1x/week. Training was performed by jumping into water (4 sets, 10 repetitions, 60 seconds rest), 50-80% body weight-load, 3 days/week, 4 weeks). Before and after training the animals were submitted a test of fatigue. After sacrifice, the right soleum muscle was removed. Third middle cuts of this muscle were made in microtome cryostat and stained through HE technique. The animals submitted to physical training (TC) and (TE) presented muscle fibers with bigger area when compared to the ones from the control group (SC and SE). Performance improvement of all experimental groups was not altered. The results suggest that physical training produces muscle hypertrophy similarly, not only in the group that received AAS, but also in the one that received mineral oil. However, the group TE presented signs of greater muscle degeneration.

Altas doses de esteróides anabólicos androgênicos (EAA) são utilizadas, sem indicação terapêutica, por indivíduos que visam aumentara força muscular ou melhorar a aparência física. Entretanto, os efeitos benéficos destas substâncias sobre o desempenho atlético são questionáveis, e sabe-se que esta prática é acompanhada de muitos efeitos colaterais. Este estudo teve por objetivo analisar as alterações histológicas e morfométricas das fibras do músculo sóleo e melhora no desempenho de ratos submetidos a um programa de treinamento físico, associado ou não à administração do esteróide anabólito decanoato de nandrolona. Os animais foram divididos em quatro grupos: sedentário + veículo (SC); treinado + veículo (TC); sedentário + EAA (SE); treinado + EAA (TE). Os animais foram tratados, por 4 semanas, com veículo (propilenoglicol, 0,2 mL/Kg) ou decanoato de nandrolona (Deca-Durabolin, 5 mg/Kg), i.m., 1 x/semana. O treinamento físico foi realizado através de saltos em meio líquido (4 séries, 10 repetições, 60 segundos de intervalo entre as séries), 50-80% do peso corporal, 3 dias/semana, 4 semanas. Antes e após o treinamento os animais foram submetidos a um teste de fadiga. Após o sacrifício, o músculo sóleo direito foi retirado. Cortes do terço médio desse músculo foram feitos em micrótomo criostato e corados pela técnica HE. Os animais submetidos ao treinamento físico (TC) e (TE) apresentaram fibras musculares com maior área, quando comparados com os animais controle (SC e SE). Não foram observadas diferenças no desempenho entre os grupos. Os resultados sugerem que o treinamento físico produz hipertrofia de forma semelhante, tanto no grupo que recebeu EAA quanto no que recebeu óleo mineral. No entanto, o grupo TE apresentou sinais de maior degeneração. / High doses of anabolic androgenic steroids (AAS) are used without therapeutic indication in order to increase the muscle power or improve the physical appearance. However the beneficial effects of AAS on the athletic performance are still questionable and it is well established that AAS abuse is associated with many detrimental side-effects. The objective of this study was to analyze the histological and morphometrical alterations of the fibers from the soleum muscle and performance improvement of rats submitted to a physical training, associated not to the administration of the anabolic steroid decanoate of nandrolone. Male Wistar rats were divided into four groups: sedentary + vehicle (SC), trained + vehicle (TC), sedentary + AAS (SE) and trained + AAS (TE). The animals were treated for 4 weeks with vehicle (propyleneglycol, 0.2 mL/Kg) or nandrolone decanoate (Deca-Durabolin, 5 mg/Kg), i.m., 1x/week. Training was performed by jumping into water (4 sets, 10 repetitions, 60 seconds rest), 50-80% body weight-load, 3 days/week, 4 weeks). Before and after training the animals were submitted a test of fatigue. After sacrifice, the right soleum muscle was removed. Third middle cuts of this muscle were made in microtome cryostat and stained through HE technique. The animals submitted to physical training (TC) and (TE) presented muscle fibers with bigger area when compared to the ones from the control group (SC and SE). Performance improvement of all experimental groups was not altered. The results suggest that physical training produces muscle hypertrophy similarly, not only in the group that received AAS, but also in the one that received mineral oil. However, the group TE presented signs of greater muscle degeneration.

Orientador: Fernanda Klein Marcondes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-19T19:10:03Z (GMT). No. of bitstreams: 1 Neves_VanderJosedas_D.pdf: 1737689 bytes, checksum: d320aa9ee9ef10e1c44b199ad2dae541 (MD5) Previous issue date: 2012 / Resumo: A associação entre o tratamento com o esteróide anabólico nandrolona e treinamento físico resistido de alta intensidade induziu hipertrofia cardíaca concêntrica, disfunção sistólica e diastólica em ratos. O objetivo deste trabalho foi avaliar se esta hipertrofia seria patológica, por meio da análise da expressão gênica de marcadores de hipertrofia cardíaca patológica (ß-miosina de cadeia pesada (ß-MHC), ?-miosina de cadeia pesada (ß-MHC), ß-actina esquelética e peptídeo natriurético atrial). Outro objetivo deste estudo foi analisar o efeito da nandrolona associada ou não ao treinamento físico sobre a pressão arterial in vivo, a eletrofisiologia cardíaca, e a população de adrenoceptores ß1 (AR-ß1) e ß2 (AR-ß2) no átrio direito de ratos. Foram utilizados 88 ratos Wistar, divididos em quatro grupos experimentais: não treinado+veículo (NTV), treinado+veículo (TV), não treinado+nandrolona (NTN), treinado+nandrolona (TN). Os animais foram tratados por 6 semanas com veículo propilenoglicol (0,2 mL/Kg) ou decanoato de nandrolona (5 mg/Kg), i.m. 2x/semana. O treinamento foi realizado por saltos em água com sobrecarga de peso variando de 50-70% do peso corporal, 5 dias/semana, por 6 semanas. Na sétima semana, os animais foram mortos por decapitação e o coração foi isolados para análise dos marcadores de hipertrofia cardíaca e da população de adrenoceptores ß atriais. Em outros animais, submetidos aos mesmos tratamentos, foi analisada a pressão arterial 1x/semana e o eletrocardiograma foi realizado no fim do período experimental. Os resultados foram comparados por ANOVA bifatorial seguido por teste de Tukey e a pressão arterial por Análise de Variância com Medidas Repetidas e com Estrutura de Variância Autoregressiva. A nandrolona diminuiu a expressão de ß-MHC nos grupos NTN (26%) e TN (42,5%) em comparação ao grupo NTV. O treinamento diminuiu a expressão de ß-MHC nos grupos TV (59,5%) e TN (22,7%) comparados ao grupo NTV. Apenas no grupo TN houve aumento de ß-actina esquelética (117,3%) e peptídeo natriurético atrial (114%) comparado a NTV. Nos grupos TV e TN, a pressão arterial sistólica, média e diastólica diminuiu em comparação aos respectivos grupos não treinados. A freqüência cardíaca diminuiu nos grupos TV e TN nas semanas 5 e 6 em comparação aos respectivos grupos não treinados. A nandrolona induziu aumento da pressão arterial sistólica nos grupos NTN e TN na quinta semana de tratamento em comparação com a primeira e segunda semanas. No eletrocardiograma, a nandrolona prolongou o intervalo QTc em 3,7% no grupo NTN e 2,7% no TN em comparação aos respectivos grupos tratados com nandrolona. A nandrolona induziu aumento de 50,1% na população de AR-ß1 no grupo NTN e 75,6% no TN em comparação ao NTV, e também induziu aumento de 66,5% na população de AR-ß2 no grupo NTN e 126,7% no TN em comparação ao NTV. Os resultados do presente trabalho mostram que a hipertrofia cardíaca induzida pela nandrolona, isoladamente, ou em associação ao treinamento físico é patológica, e sugerem que as alterações na população de adrenoceptores ß podem representar um mecanismo compensatório aos efeitos desencadeados pela nandrolona sobre o miocárdio hipertrofiado / Abstract: The nandrolone or its association with physical training induced concentric cardiac hypertrophy associated with systolic and diastolic dysfunction in the heart of rat. In this way, to complement these results, the objective of this study was to evaluate the influence of nandrolone and resistance training on cardiac hypertrophy, the gene expression of pathological cardiac hypertrophy markers (ß-myosin heavy chain (ß-MHC), ß-myosin heavy chain (ß-MHC), ß-skeletal actin and atrial natriuretic peptide), blood pressure in vivo, cardiac electrophysiology, and the population of ß1-adrenoceptor (AR-ß1) and ß2 (ß2-AR) in right atrium of 88 Wistar rats, which were divided into four groups: non trained+vehicle (NTV), Trained+vehicle (TV), non trained+nandrolone (NTN), trained+nandrolone (TN). The animals were treated for 6 weeks with vehicle propylene glycol (0.2 mL/kg) or nandrolone decanoate (5 mg/kg), i.m. 2x/week. The training was carried out by jumping into water with overweight ranging from 50-70% of body weight, 5 days/week for 6 weeks. After sacrifice of animals, were performed the analysis of cardiac hypertrophy markers of ß adrenoceptors population. In other animals underwent the same treatment, blood pressure was analyzed 1x/semana and electrocardiogram was performed at the end of trial period. The results were calculated by two-way ANOVA followed by Tukey test and blood pressure by Analysis of Variance with Repeated Measures of Structure of Self-regressive Variance. The results showed cardiac hypertrophy 9% higher in the TV group and 8% for NTN compared to NTV, and this effect was potentiated in TN group. The nandrolone decreased the expression of ß-MHC in the NTN group (26%) and TN (42.5%), both compared to NTV. Training decreased the expression of ß-MHC in TV group (in 59.5%) and TN (22.7%) compared to NTV. Only in the TN group, both ß-skeletal actin (117.3%) and atrial natriuretic peptide (114%) were increased compared to NTV. In TV and TN groups, systolic, mean and diastolic blood pressures were decreased compared to the respective non trained groups. The heart rate decreased in the groups TV and TN in the weeks 5 and 6 in comparison to the respective groups NTV and NTN. The nandrolone increased systolic blood pressure in TN and NTN groups in the fifth week of treatment compared to the first and second weeks. The electrocardiogram analysis shown that nandrolone prolonged QTc interval by 3.7% in the NTN group and 2.7% in TN compared to respective groups NTV and TV. The nandrolone induced an increase of 50.1% in the population of AR-ß1 on NTN group and 75.6% in TN compared to NTV, and also increased 66.5% in the ß2-AR population in the NTN group and 126,7% in TN compared to NTV. In conclusion, the results of this study confirm that cardiac hypertrophy induced by only nandrolone or in combination with physical training is pathological, and suggest that changes in the population of ß-adrenoceptors are an attempt of right atrium to compensate the negative effects of nandrolone on the hypertrophied myocardium / Doutorado / Fisiologia Oral / Doutor em Odontologia

To compare the efficacy and safety of nandrolone decanoate and calcium (NDC) with those of calcium alone (CAL) in men with idiopathic osteoporosis, a 12-month, randomized, prospective, controlled study, was performed in an outpatient clinic. Twenty-one men with idiopathic osteoporosis (as determined by radiological and dual energy x-ray absorptiometry findings) were randomly allocated to either 50 mg nandrolone decanoate intramuscularly (im) weekly and 1,000 mg oral calcium carbonate daily (NDC group) or to 1,000 mg oral calcium carbonate daily (CAL group). Bone densitometry (total body, left femur, and lumbar spine), serum, and urine biochemical parameters were measured at 3-month intervals. In the NDC group, bone mineral density initially increased, reached a plateau, and then decreased to near baseline levels at 12 months. Increases in lean muscle mass mirrored these changes. Free and total testosterone significantly decreased. Hemoglobin increased in all patients in this group. Patients in the CAL group exhibited no significant change in either total body or bone mineral density or biochemical parameters. Thus, nandrolone decanoate, 50 mg im weekly, transiently increases the bone mass of men with idiopathic osteoporosis in this preliminary study. Careful monitoring is necessary.

<p>Supratherapeutic doses of anabolic androgenic steroids (AASs) are administered, not only as performance-enhancing drugs in the world of sports, but also in order to modify behaviour. AAS abusers are at risk of developing serious physical and psychological side effects such as dependence and aggressive behaviour. The aim of this thesis was to investigate the impact of supratherapeutic doses of nandrolone decanoate after subchronic administration on dopamine and serotonin pathways involved in drug dependence and aggression, in the male rat brain.</p><p>Adult male Sprague-Dawley rats received intramuscular injections of nandrolone decanoate (3 or 15 mg/kg) or vehicle once daily for 14 days. Nandrolone decanoate pre-exposure abolished the effect of amphetamine on the 3,4-dihydroxyphenylacetic acid (DOPAC) tissue level in the hypothalamus and on the DOPAC/dopamine ratio in the hypothalamus and the hippocampus. A significant decrease of the basal extracellular DOPAC and homovanillic acid (HVA) levels could be detected in the nucleus accumbens, which remained low during the first hour following the amphetamine challenge. Nandrolone decanoate significantly reduced the activity of both monoamine oxidase A and B (MAO-A and -B) in the caudate putamen and amygdala. The gene transcript levels of MAO-B, and the dopamine D1 and D4 receptors were altered in limbic regions. No changes in transcriptional levels could be detected among the serotonin receptor genes examined. However, the density of the serotonin transporter protein was elevated in a range of aggression-related brain regions.</p><p>Taken together, subchronic administration of nandrolone decanoate causes dopaminergic and serotonergic dysregulations in distinct brain regions. These areas of the brain are involved in the development of drug dependence and expression of impulsive and aggressive behaviours. These results may contribute to explain some of the behavioural changes often reported in AAS abusers, such as polydrug use and impaired impulse control.</p>

O decanoato de nandrolona é um esteróide anabólico-androgênico (EAA), derivado da testosterona, utilizado de maneira abusiva por indivíduos procurando ganho de força física ou apenas efeitos estéticos. Doses suprafisiológicas desses compostos têm sido associadas a efeitos psiquiátricos adversos, especialmente episódios de impulsividade e aumento no comportamento agressivo. Considerando o desconhecimento dos mecanismos neurais envolvidos nessa desinibição comportamental, nós investigamos a integridade da transcrição de componentes do sistema serotoninérgico (intimamente relacionados à expressão de comportamentos emocionais) em diversas áreas cerebrais de camundongos sob a administração prolongada de nandrolona. Camundongos machos adultos da linhagem C57Bl/6J receberam uma injeção subcutânea diária de 15 mg/kg de decanoato de nandrolona durante 28 dias. Diferentes grupos de animais foram utilizados para a análise de comportamentos emocionais e para a quantificação da expressão de genes relacionados à serotonina (5-HT), utilizando a transcrição reversa do RNA associada à técnica de PCR em tempo-real. Os camundongos tratados apresentaram um aumento na massa corporal, hiperatividade motora e aumento de comportamentos relacionados à ansiedade em ambientes novos. A imobilidade avaliada no teste de nado forçado apresentou-se reduzida. Os animais que receberam a nandrolona se mostraram mais agressivos e impulsivos para iniciar o ataque aos camundongos oponentes, no modelo de residenteintruso. O EAA induziu uma redução significante na quantidade de transcritos da maioria dos receptores pós-sinápticos de 5-HT investigados na amígdala e no córtex pré-frontal. A expressão do gene do receptor 5-HT1B (reconhecidamente envolvido com as alterações comportamentais observadas) estava também reduzida no hipocampo e hipotálamo. No mesencéfalo, região onde se encontram os corpos neuronais dos neurônios serotoninérgicos que inervam o sistema límbico e demais áreas cerebrais, não se observou nenhuma alteração na expressão dos genes relacionados aos receptores serotoninérgicos pré-sinápticos. Os transcritos do transportador e da enzima de síntese de 5-HT, indicadores da integridade serotoninérgica pré-sináptica, também não se apresentaram alterados. Dessa maneira, concluímos que o efeito de altas doses do EAA decanoato de nandrolona em camundongos confirma os dados encontrados em literatura quanto à desinibição comportamental observada em usuários abusivos humanos. Nosso modelo também foi eficiente em mostrar pela primeira vez alterações moleculares induzidas por este EAA. A redução generalizada na expressão dos genes de receptores de 5-HT na amígdala e córtex pré-frontal sugere essas áreas, pós-sinápticas ao sistema serotoninérgico, como críticas nos efeitos induzidos pelo EAA. Nosso trabalho também sugere um papel importante para o receptor 5-HT1B na desinibição comportamental observada / Nandrolone decanoate is a highly abused anabolic-androgenic steroid (AAS) by individuals looking for gains in physical strength or body appearance. Supraphysiological doses of this testosterone synthetic derivative have been associated with many physical and psychiatric adverse effects, especially reported episodes of impulsiveness and overt aggressive behavior. Since the neural mechanisms underlying AAS-induced behavioral disinhibition are unknown, we investigated the integrity of serotonergic system transcription in several brain areas of mice under prolonged nandrolone administration. Male C57Bl/6J mice received 15 mg/kg of nandrolone decanoate subcutaneously once daily for 28 days, and different sets of animals were used to investigate motor and emotion-related behaviors or 5-HT-related gene expression by qRT-PCR. AAS-injected mice had increased body weight, were hyperactive and displayed more anxious-like behaviors in novel environments. They exhibited reduced immobility in the forced swim test, higher probability of being aggressive and elevated impulsivity to attack the opponent. AAS induced substantial reduction in the transcription of most postsynaptic 5-HT receptors investigated in the amygdala and prefrontal cortex. Interestingly, 5-HT1B mRNA was further reduced in the hippocampus and hypothalamus. At the midbrain level, there was no alteration in 5- HT receptors, transporter or synthetic enzyme gene transcription. In conclusion, high doses of AAS nandrolone in male mice recapitulate the behavioral disinhibition observed in abusers. Furthermore, they are associated with overall decrease in 5-HT receptor gene expression in the amygdala and prefrontal cortex, implicating these areas as critical sites for AASinduced effects and indicating a role for the 5-HT1B receptor in this behavioral disinhibition