Anabolic Androgenic Steroids Nandrolone Decanoate Research Articles

The anabolic androgenic steroid nandrolone decanoate disrupts redox homeostasis in liver, heart and kidney of male Wistar rats.

The abuse of anabolic androgenic steroids (AAS) may cause side effects in several tissues. Oxidative stress is linked to the pathophysiology of most of these alterations, being involved in fibrosis, cellular proliferation, tumorigenesis, amongst others. Thus, the aim of this study was to determine the impact of supraphysiological doses of nandrolone decanoate (DECA) on the redox balance of liver, heart and kidney. Wistar male rats were treated with intramuscular injections of vehicle or DECA (1 mg.100 g−1 body weight) once a week for 8 weeks. The activity and mRNA levels of NADPH Oxidase (NOX), and the activity of catalase, glutathione peroxidase (GPx) and total superoxide dismutase (SOD), as well as the reduced thiol and carbonyl residue proteins, were measured in liver, heart and kidney. DECA treatment increased NOX activity in heart and liver, but NOX2 mRNA levels were only increased in heart. Liver catalase and SOD activities were decreased in the DECA-treated group, but only catalase activity was decreased in the kidney. No differences were detected in GPx activity. Thiol residues were decreased in the liver and kidney of treated animals in comparison to the control group, while carbonyl residues were increased in the kidney after the treatment. Taken together, our results show that chronically administered DECA is able to disrupt the cellular redox balance, leading to an oxidative stress state.

Nandrolone decanoate increases satellite cell numbers in the chicken pectoralis muscle.

The anabolic androgenic steroid nandrolone decanoate has minimal androgenic effects and, thus, is widely used to induce muscle hypertrophy in both patients and athletes. Although increases in satellite cell numbers and satellite cells giving rise to new myonuclei are associated with hypertrophy in many experimental models, the relationship between nandrolone and satellite cells is poorly understood. Here we test the hypothesis that nandrolone administration is associated with an increase in satellite cell numbers in muscle. Nandrolone was injected at weekly intervals for four weeks into the right pectoralis muscle of female white leghorn chickens aged 63 days post hatch. Age/size/sex matched control birds received saline injections. The contralateral pectoralis was excised for study from each control and nandrolone treated bird. An antibody against Pax7 and immunocytochemical techniques were used to identify satellite cells. Nandrolone significantly increased mean pectoralis mass by approximately 22%, and mean fiber diameter by about 24%. All satellite cell indices that were quantified increased significantly in chicken pectoralis with administration of nandrolone. Nandrolone injected birds had on average higher satellite cell frequencies (#SC nuclei/all nuclei within basal lamina), number of satellite cells per millimeter of fiber, and satellite cell concentrations (closer together). Myonuclei were further apart (less concentrated) in nandrolone injected muscle. However, an overall increase in myonuclear numbers was revealed by a significantly greater mean number of myonuclei per millimeter of fiber in nandrolone injected muscle. Our results suggest that satellite cells may be key cellular vectors for nandrolone induced muscle fiber hypertrophy.

The effect of nandrolone decanoate on liver of rabbitsusing histological and ultrasound methods

Objective: To compare the effects of nandrolone decanoate on the liver structure in male and female rabbits using histological and ultrasound examinations.Materials and methods: Forty-eight adult rabbits were divided into two groups, male and female groups, each included 24 adult healthy rabbits. The male group was subdivided into 4 subgroups, group A was the control group which received only normal saline, group B was given nandrolone decanoate 2mg/kg body weight, group C was given 4 mg/kg body weight of nandrolone decanoate, while group D was given 6 mg/kg body weight of the drug. The female group was also subdivided into 4 subgroups, group A1 was the control group, group B1 was given 2 mg/kg body weight, group C1 was given 4 mg/kg body weight, group D1 was given 6 mg/kg body weight of nandrolone decanoate.Results: All treated groups of both sexes showed a significant increase in body and liver weights in addition to dose related pathological changes ranging from mild to severe form, including vacuolar degeneration and fatty degenerative changes of hepatocytes. In addition, there was a dilatation and congestion of sinusoids, central venules and portal veins with mononuclear inflammatory cells infiltration. Focal areas of necrosis with chronic inflammatory cells infiltration were also noticed in different hepatic lobules. In spite of these histological changes in the liver no abnormal ultrasound findings of the liver were noticed.Conclusion: These changes indicate that the histological effects of the anabolic androgenic steroid nandrolone decanoate on the liver of adult male and female rabbits is the same in both sexes, but the treated female rabbit groups of medium and high doses (C1 and D1) showed more increase in body weight than male rabbit groups. There is no correlation between histological and ultrasound findingsKeywords: Nandrolone decanoate, liver histology, rabbits.

Nandrolone decanoate administration dose-dependently affects the density of kappa opioid peptide receptors in the rat brain determined by autoradiography

The kappa opioid receptor ligand [(3)H]CI-977 was used to autoradiographically determine the density of kappa opioid receptors in the male rat brain following chronic treatment with the anabolic androgenic steroid nandrolone decanoate at two different doses. As compared to controls, significantly lower densities of the kappa opioid receptor were encountered after two weeks of high dose nandrolone decanoate (15 mg/kg) in the nucleus accumbens shell (16%), lateral hypothalamic area (36%), ventromedial hypothalamic nucleus (37%), dorsomedial hypothalamic nucleus (49%), central amygdaloid nucleus, capsular part (28%), lateral globus pallidus (35%) and in the stria terminalis (24%). Furthermore, an up-regulation of the receptor level was observed in the caudate putamen (18%) and in the dorsal endopiriform nucleus (23%). These alterations in the kappa opioid receptor expression are possibly attributed to a previously observed pronounced impact of nandrolone decanoate on the dynorphinergic system and could also include involvement of the dopaminergic reward system.

The anabolic androgenic steroid nandrolone decanoate affects mRNA expression of dopaminergic but not serotonergic receptors

The anabolic androgenic steroid nandrolone decanoate affects mRNA expression of dopaminergic but not serotonergic receptors

The anabolic androgenic steroid nandrolone decanoate affects mRNA expression of dopaminergic but not serotonergic receptors

The abuse of anabolic androgenic steroids (AASs) at supratherapeutic doses is a problem not only in the world of sports, but also among non-athletes using AASs to improve physical appearance and to become more bold and courageous. Investigations of the possible neurochemical effects of AAS have focused partially on the monoaminergic systems, which are involved in aggressive behaviours and the development of drug dependence. In the present study, we administered nandrolone decanoate (3 or 15 mg/kg/day for 14 days) and measured mRNA expression of dopaminergic and serotonergic receptors, transporters and enzymes in the male rat brain using quantitative real-time polymerase chain reaction. Expression of the dopamine D1-receptor transcript was elevated in the amygdala and decreased in the hippocampus while the transcript level of the dopamine D4-receptor was increased in the nucleus accumbens. No changes in transcriptional levels were detected among the serotonin-related genes examined in this study. The altered mRNA expression of the dopamine receptors may contribute to some of the behavioural changes often reported in AAS abusers of increased impulsivity, aggression and drug-seeking.

Administration of the anabolic androgenic steroid nandrolone decanoate to female rats causes alterations in the morphology of their uterus and a reduction in reproductive capacity

Objective The aim of the present investigation was to characterize the effects of supraphysiological doses of the anabolic androgenic steroid nandrolone decanoate (ND) on the fertility of female rats, as well as on the morphology of their uterus. Study design Female Wistar rats ( n = 15) received a subcutaneous injection of ND (15 mg/kg) once daily during a 2-week period, while the control animals ( n = 10) were administered vehicle alone (arachidis oleum) in the same manner. Estrus behavior was evaluated 4 weeks after termination of this treatment and in cases where signs of receptivity were present, the female rat was given the opportunity to copulate with a male. After breeding, the female animals were sacrificed and their uteri examined histomorphologically. Results All ND-treated animals exhibited abnormal vaginal smears, whereas all of the control smears were normal. Most (73%) of the treated females demonstrated normal estrus behavior (i.e., willingness) on the day of mating, but none got pregnant; whereas all of the control rats became pregnant. The female rats receiving the ND showed an enhanced rate of weight gain and the myometrium thickness of their uteri was significantly increased, while the endometrium was significantly thinner. Furthermore, ND caused a significant proportion of the treated animals to display tortuous and irregularly branching endometrial glands, as well as a lack of the physiologically normal infiltration of eosinophilic leukocytes into the endometrium (endometrial eosinophilic homing), a finding that has not been reported previously. Conclusion The present findings indicate that high doses of ND cause morphological and physiological alterations in the uterus of female rats that are associated with a suppression of their reproductive capacity.

Administration of the anabolic androgenic steroid nandrolone decanoate affects substance P endopeptidase-like activity in the rat brain

The effect of the anabolic androgenic steroid, nandrolone decanoate, on substance P endopeptidase-like activity was examined in adult male Sprague–Dawley rats. Nandrolone decanoate (15 mg/kg day) or oil vehicle (sterile arachidis oleum) were administered by intramuscular injections during 14 days. Substance P endopeptidase, a predominantly cytosolic enzyme, generates the bioactive N-terminal fragment substance P 1–7 from the enzyme substrate substance P. Nandrolone decanoate significantly reduced the substance P endopeptidase-like activity compared to control animals in hypothalamus (43% reduction), caudate putamen (44%), substantia nigra (32%) and the ventral tegmental area (27%). It was previously reported that both hypothalamus and caudate putamen contained significantly higher levels of substance P after nandrolone administration. The higher concentration of substance P in these regions could to an extent be attributed to the reduction in substance P endopeptidase-like activity. This result elucidates the important role of peptidase activity in the regulation of the substance P transmitter system. The present study provides additional support for the hypothesis that alterations in the substance P system in certain brain areas may contribute to some of the personality changes reported in connection with AAS abuse.

Anabolic androgenic steroid affects social aggression and fear-related behaviors in male pair-housed rats

This study examines the effect of chronic administration of the anabolic androgenic steroid nandrolone decanoate (ND) on dominant and subordinate male rats in a pair-housed condition. Pair-housed rats were assessed for dominance status based on their behavior and alterations in body weights. Throughout the study the rats were allowed limited social interactions on a daily basis. At all other times, a Plexiglas divider kept the rats separated, allowing olfactory and visual contact between the cage mates while preventing significant physical contact. One week into the study all subjects were subcutaneously implanted with a pellet that continuously infused either ND (15 mg/kg/day) or placebo for 21 days. Following the pellet implant, behavioral tests including reassessment for dominance status, and a conditioned fear test were conducted over a period of approximately 2 months to investigate possible long-term changes. The main finding is that during the allowed social interactions, the dominant ND-pretreated rats spent more time on highly aggressive behaviors than the dominant placebo-treated rats. In addition, the probability for highly aggressive behaviors was maintained for the ND-treated rats throughout the study, whereas it was decreased for the placebo-treated rats. The ND-treated subordinate rats showed less fear in a potential threatening situation compared to placebo-treated controls. These findings support the relatively long-term behavioral changes that have been seen in humans after abuse of ND and other anabolic androgenic steroid compounds.

The impact of chronic nandrolone decanoate administration on the NK1 receptor density in rat brain as determined by autoradiography

Adult male Sprague–Dawley rats were treated with the anabolic androgenic steroid nandrolone decanoate (15 mg/kg day) or oil vehicle (sterile arachidis oleum) during 14 days. The effect on the densities of the neurokinin NK1 receptor in brain was examined with autoradiography. An overall tendency of attenuation of NK1 receptor density was observed after completed treatment with nandrolone decanoate. The density of the NK1 receptor was found to be significantly lower compared to control animals in the nucleus accumbens core (37% density reduction), in dentate gyrus (26%), in basolateral amygdaloid nucleus (23%), in ventromedial hypothalamic nucleus (36%), in dorsomedial hypothalamic nucleus (43%) and finally in the periaqueductal gray (PAG) (24%). In the cortex region, no structures exhibited any significant reduction of NK1 receptor density. This result provides additional support to the hypothesis that substance P and the NK1 receptor may be involved as important components that participate in mediating physiological responses including the adverse behaviors often associated with chronically administrated anabolic androgenic steroids in human.

Amphetamine-induced aggression is enhanced in rats pre-treated with the anabolic androgenic steroid nandrolone decanoate

Aggression is one of the most commonly reported psychiatric side effects among anabolic–androgenic steroids (AAS) users. Furthermore, anecdotal stories say the aggression is even more profound when a current, or former, AAS-user consumes other drugs of abuse such as amphetamine and alcohol. In the present study, we examined the effect of amphetamine on defensive reactivity and defensive aggression in Sprague–Dawley rats after chronic AAS treatment (daily intramuscular [i.m.] injections with 15 mg/kg nandrolone decanoate [ND] for 14 days). Defensive reactions in rodents occur in response to a real threat, but also to perceived provocation, for example, elicited by innocuous stimuli as reaction towards the experimenter. The defensive reactivity and aggression test employed in this study evaluates each rat's reaction towards four different stimuli (I: approach of a rod; II: startle to an air puff; III: poking with a rod at the flanks, and IV: capturing with a gloved hand) at two different occasions. Immediately following the ND treatment period, no change in the defensive response was found. Nevertheless, an amphetamine challenge given 3 weeks after the last ND or vehicle injection induced a marked increased defensive aggressive response in the ND, compared to vehicle-pre-treated rats. Both ND- and vehicle-pre-treated rats receiving amphetamine were found to be more aggressive than comparable groups receiving a saline injection. It can be concluded that pre-treatment with ND modulates the behavioral response to amphetamine and induces long lasting changes in the behavioral response.

Anabolic androgenic steroid nandrolone decanoate reduces hypothalamic proopiomelanocortin mRNA levels

Supratherapeutical doses of anabolic androgenic steroids (AASs) have dramatic effects on metabolism in humans, and also inhibit feeding and reduce the rate of body weight gain in rats. In order to test the hypothesis that the AAS metabolic syndrome is accompanied by alterations in the central melanocortin system, we evaluated body weight, food intake and hypothalamic agouti-related protein (AgRP) and proopiomelanocortin (POMC) mRNA levels following administration of different doses of the anabolic androgenic steroid nandrolone decanoate. In order to distinguish changes induced by the steroid treatment per se from those resulting from the reduced food intake and growth rate, we also compared the effect of nandrolone decanoate on AgRP and POMC mRNA expression with both normally fed, and food restricted control groups. We here report that administration of nandrolone specifically reduces arcuate nucleus POMC mRNA levels while not affecting the expression level of AgRP. The effect on POMC expression was not observed in the food restricted controls, excluding the possibility that the observed effect was a mere response to the reduced food intake and body weight. These results raise the possibility that some of the metabolic and behavioural consequences of AAS abuse may be the result of alterations in the melanocortin system.

Nandrolone treatment decreases the level of rat kidney alpha(1B)-adrenoceptors.

Abuse of anabolic androgenic steroids (AAS) is associated with serious side effects, such as hypertension and fluid retention. Renal alpha(1)- and alpha(2)-adrenoceptors are implicated in the regulation of blood pressure and fluid balance. In the present study, the levels of renal alpha(1A)-, alpha(1B)-, alpha(2A)- and alpha(2B)-adrenoceptors, and spleen alpha(1B)-adrenoceptors, were quantified in tissue membranes from rats treated with the AAS nandrolone decanoate (15 mg/kg) for 14 days. The radioligands used were [(3)H]-prazosin and [(3)H]-RX821002. The nandrolone treatment caused a 50% reduction of kidney alpha(1B)-adrenoceptors (from 15 fmol/mg protein in control rats to 6.5 fmol/mg protein in treated rats). In contrast, the levels of kidney alpha(1A)-, alpha(2A)- and alpha(2B)-, and spleen alpha(1B)-adrenoceptors were unaffected. These results raise the possibility that a decreased level of kidney alpha(1B)-adrenoceptors may cause some of the effects observed on blood pressure and fluid balance in heavy abuse of AAS.

The anabolic–androgenic steroid nandrolone induces alterations in the density of serotonergic 5ht 1b and 5ht 2 receptors in the male rat brain

Anabolic-androgenic steroids (AAS) are partly misused by males in order to become brave and intoxicated and these agents are highly associated with psychosis, disinhibition, aggression and acts of violence. Since such behavioral states have been related to an imbalanced serotonergic system and the involvement of the serotonergic 5HT 1B and the 5HT 2 receptors, it was important to discern the impact of AAS on these receptors. The objective of our study was to investigate the effects of 2 weeks of treatment with the AAS nandrolone decanoate at three different doses (1, 5, 15 mg/kg/day) on the total specific binding of the radioligands [ 125I]-(±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (5HT 2 receptors) by autoradiography. All doses caused a significant down-regulation of the 5HT 1B receptor density in the hippocampal CA 1 and in the medial globus pallidus and a significant up-regulation of the 5HT 2 receptor density in the nucleus accumbens shell. Alterations in receptor density were also observed in the lateral globus pallidus, ventromedial hypothalamus, the amygdala and in the intermediate layers of various cortex regions. In conclusion, serotonergic 5HT 1B or 5HT 2 receptors are likely to play important roles in mediating observed emotional states and behavioral changes among AAS abusers.

Dopaminergic effects after chronic treatment with nandrolone visualized in rat brain by positron emission tomography

Anabolic–androgenic steroids (AAS) have recently been shown to induce neurochemical alterations in areas of the male rat CNS related to behavioural changes that have been observed among AAS misusers. In the present study, positron emission tomography (PET) is suggested as a suitable in vivo method in order to visualize the density of the dopamine transporter ([ 11C]-FE-β-CIT) as well as the dopamine D 1-like ([ 11C]-(+)-SCH23390) and the D 2-like receptors ([ 11C]-raclopride) in the male rat brain. Chronic treatment with the AAS nandrolone decanoate (15 mg/kg/day for 14 days) caused an up-regulation of the binding potential of the dopamine transporter in the striatum.