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PubMed2005

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.

Aggression↗
PubMed2003

Chronic administration with nandrolone decanoate induces alterations in the gene-transcript content of dopamine D(1)- and D(2)-receptors in the rat brain.

Some adolescent and young males are engaged in misuse of anabolic-androgenic steroids (AASs) in connection with multiple drug use, in order to become intoxicated and brave, apart from currently known motives connected to sports performance and physical appearance. Recent studies suggest that alterations in neurobiological circuits implicated in the regulation of reward-related learning, aggression and motoric behavior underlie the behavioral changes associated with AAS misuse. We have previously shown that AASs induce alterations in dopamine receptor densities. The aim of the present study was to investigate if these effects could be attributed to altered mRNA content for tyrosine hydroxylase, L-amino acid decarboxylase, dopamine D(1)- and dopamine D(2)-receptor as measured by in situ hybridisation. Male Sprague-Dawley rats were subjected to 2 weeks of treatment with daily intramuscular injections of the AAS nandrolone decanoate at three different doses (1, 5 and 15 mg/kg/day). Results of the in situ hybridization showed that the mRNA content of the dopamine D(1)-receptor subtype was significantly reduced at all doses in the caudate putamen and at the highest doses in the nucleus accumbens shell. The mRNA expression of the dopamine D(2)-receptor was significantly increased at the two lowest doses in the caudate putamen and the nucleus accumbens shell. In conclusion, nandrolone has been shown to affect the expression of gene transcripts of dopaminergic receptors possibly implicated in underlying mechanisms of reward-related behavioral changes among AAS misusers.

Anabolic Agents↗
PubMed1999

Esterification of decanoic acid during supercritical fluid extraction employing either methanol-modified carbon dioxide or a methanol trap.

The methylation of decanoic acid during the supercritical fluid extraction process was investigated. It was found that the majority of the methylation occurred not during the extraction, but during the collection step, in the presence of methanol. Increasing dynamic extraction time (and hence collection time) from 0 to 60 min increased acid to ester conversions from 2% to 4%. The addition of HCl as a catalyst to the reaction increased the reaction rate 10-fold, and resulted in 88% conversion to the methyl ester within 30 min, without any detrimental effects on the chromatographic system. Higher collection temperatures appeared to increase conversion, but decreased methyl ester collection efficiency.

Carbon Dioxide↗
PubMed2000

The effects of nandrolone decanoate on cocaine-induced kindling in male rats.

Use and abuse of various controlled substances in recent years has reached alarming levels. Among these are cocaine and anabolic steroids. The two contrasting types of drug have common sites of action within the limbic system of the central nervous system. The ability of cocaine to provoke seizures is well documented, and sex hormones also have been shown to alter seizure types and characteristics. This project studied the consequences of co-administration of cocaine and a representative anabolic-androgenic steroid, nandrolone decanoate. Specifically, the effects of nandrolone on cocaine-induced kindling of seizures were examined. Nandrolone was shown to increase seizure rate when given in high (20mg twice weekly) intermittent doses. No statistically significant differences were observed with low (2mg) daily doses of nandrolone. The results support the hypothesis that an androgen may interact so as to modify the pattern of cocaine-related kindling. However, the potential of either pharmacodynamic and/or pharmacokinetic mechanism(s) for this interaction exists, and the nature of these interactions remains to be fully elucidated.

Anabolic Agents↗
PubMed2000

Effects of the androgenic anabolic steroid, nandrolone decanoate, on adrenocorticotropin hormone, corticosterone and proopiomelanocortin, corticotropin releasing factor (CRF) and CRF receptor1 mRNA levels in the hypothalamus, pituitary and amygdala of the rat.

There is increasing abuse of androgenic anabolic steroids (AAS) by non-athletes. AAS abuse has been associated with psychiatric symptoms such as mania, major depression and aggression and the development of dependence. Little is known about the effects of AAS on hypothalamic-pituitary-adrenal axis function or corticotropin releasing factor, which may be involved in mediating some of the psychiatric symptoms associated with AAS abuse. Male Sprague-Dawley rats received one daily intra-muscular injection of the AAS nandrolone decanoate (ND, 15 mg/kg) or vehicle for 3 days. Animals were sacrificed either 1 h or 24 h after the last injection, brain regions dissected and trunk blood collected. Corticotropin releasing factor (CRF), CRF receptor1 (CRF-R1) and proopiomelanocortin (POMC) mRNAs were measured with solution hybridization/RNase protection. Circulating levels of corticosterone and adrenocorticotropin hormone (ACTH) were determined using radioimmunoassays. One hour following the last injection, ND significantly increased circulating levels of both corticosterone and ACTH levels. In the amygdala, CRF mRNA levels were unchanged 1 h after the last injection of ND but were significantly reduced at 24 h. The same was found for hypothalamic POMC. No significant AAS effects were observed on: hypothalamic CRF mRNA; POMC mRNA in the amygdala or CRF R1 mRNA in the anterior pituitary.

Adrenocorticotropic Hormone↗
PubMed2000

A physical, chemical, and mechanical study of lumbar vertebrae from normal, ovariectomized, and nandrolone decanoate-treated cynomolgus monkeys (Macaca fascicularis).

Ovariectomized cynomolgus monkeys have previously been investigated as a nonhuman primate model of postmenopausal osteoporosis (Jerome et al., Bone Miner 9:527-540; 1994). In the present study, Fourier transform infrared microspectroscopy (FTIRM) was used to verify that differences in bone mineral quality and quantity in the vertebrae of mature intact (INT) and ovariectomized (ovx) monkeys were analogous to those seen in osteoporotic and nondiseased human bones. FTIRM spectra were acquired from 15 trabeculae per vertebra from three ovx and three INT adult monkeys (mean age 8 years). These spectra were compared with those of both trabecular and previously reported osteonal bone obtained from 3 "normal" and 11 postmenopausal osteoporotic human subjects. While variations in the mineral:matrix ratio (mineral content), carbonate:phosphate ratio, and crystallinity are typical for trabecular bone from iliac crests of normal human subjects, the values of these parameters were relatively static for trabecular bone from postmenopausal osteoporotic human subjects. In general, trabecular bone from postmenopausal osteoporotic human subjects exhibited decreased mineral content (1.0 +/- 0.5 vs. 2.9 +/- 0.6), increased crystallinity, and increased carbonate:phosphate relative to controls. Similarly, trabecular bone from ovariectomized monkeys exhibited lower mineral content (5.8 +/- 0.2) compared with the INT group (6.2 +/- 0.2; p </= 0.05) and contained larger/more perfect apatite crystals (increased crystallinity) with increased carbonate:phosphate ratios. Variations in absolute values were attributable to site differences (ilium vs. vertebrae). To appreciate the importance of mineral properties on mechanical properties, compression testing was performed using cores of monkey L-3 and L-4 vertebral bodies from a separate group of monkeys. Treating monkeys with the anabolic steroid nandrolone decanoate (ND) immediately after ovariectomy and for the next 24 months (ND group), or beginning 12 months after ovariectomy (dND group), increased the ultimate stress compared with an ovx treatment group, despite large interanimal variations in bone architecture and mechanical properties. These data support the hypothesis that ovariectomized adult monkeys are an excellent model for postmenopausal osteoporosis, and can be used for the evaluation of therapeutic modalities.

Animals↗
PubMed2006

Solution structures of spinach acyl carrier protein with decanoate and stearate.

Acyl carrier protein (ACP) is a cofactor in a variety of biosynthetic pathways, including fatty acid metabolism. Thus, it is of interest to determine structures of physiologically relevant ACP-fatty acid complexes. We report here the NMR solution structures of spinach ACP with decanoate (10:0-ACP) and stearate (18:0-ACP) attached to the 4'-phosphopantetheine prosthetic group. The protein in the fatty acid complexes adopts a single conformer, unlike apo- and holo-ACP, which interconvert in solution between two major conformers. The protein component of both 10:0- and 18:0-ACP adopts the four-helix bundle topology characteristic of ACP, and a fatty acid binding cavity was identified in both structures. Portions of the protein close in space to the fatty acid and the 4'-phosphopantetheine were identified using filtered/edited NOESY experiments. A docking protocol was used to generate protein structures containing bound fatty acid for 10:0- and 18:0-ACP. In both cases, the predominant structure contained fatty acid bound down the center of the helical bundle, in agreement with the location of the fatty acid binding pockets. These structures demonstrate the conformational flexibility of spinach ACP and suggest how the protein changes to accommodate its myriad binding partners.

Acyl Carrier Protein↗
PubMedDate not supplied

Effects of the peroxisome proliferator perfluoro-n-decanoic acid on hepatic gluconeogenesis and glycogenesis: a 13C NMR investigation.

Carbon-13 NMR spectroscopy was used to study the effects of the peroxisome proliferator perfluoro-n-decanoic acid (PFDA) on hepatic carbohydrate metabolism in male Fischer-344 rats. The data indicate that PFDA-treated rats display an inhibition in hepatic [1-13C]glucose and [3-13C]alanine utilization on day 5 posttreatment. PFDA rats show hepatic mean glucose and alanine intensities which are significantly greater (ca. 10-100%) than controls. With [1-13C]-glucose as substrate, PFDA rats show severe to complete inhibition in glycogenesis on days 3 and 5 posttreatment. With [3-13C]alanine as substrate, both groups show functional gluconeogenesis and glycogenesis; however, treated rats show a more transient and less intense C1-glycogen resonance relative to control. These data suggest that PFDA inhibits either the hepatocellular transport of glucose and/or its phosphorylation by glucokinase. The effect of PFDA on TCA cycle activity was determined by monitoring the flow of [3-13C]alanine into glutamate. The relative activity of pyruvate carboxylase (PC) versus pyruvate dehydrogenase (PDH) is represented by the ratio of the glutamate NMR signal intensities (C2 + C3)/C4. PFDA rats show a lower (C2 + C3)/C4 glutamate ratio, suggesting greater relative activity of PDH versus PC in PFDA rats relative to controls. Differences in PDH activity may arise from differences in lipolytic activity. Our data suggest a dysfunction in fatty acid metabolism in PFDA rats and corroborate other studies which show that PFDA inhibits fatty acid oxidation.

Alanine↗
PubMedDate not supplied

Effect of the peroxisome proliferator perfluoro-n-decanoic acid on glucose transport in the isolated perfused rat liver.

The perfluorinated carboxylic acid, perfluoro-n-decanoic acid (PFDA), is a known peroxisome proliferator which displays toxicity in rodents. Using a paired-tracer first-pass extraction technique, the effect of PFDA on hepatic glucose transport was determined in the isolated perfused rat liver. In brief, livers isolated from PFDA-treated and control rats on day 5 posttreatment were administered the radiolabeled glucose analog, 3-O-[14C]methyl-D-glucose ([14C]3-O-MG) in addition to [fructose-1-3H(N)]sucrose ([3H]sucrose), which served as a measure of extracellular volume. Hepatic glucose transport was calculated from the change in the ratio [14C]3-O-MG/[3H]sucrose during passage through the liver. Data from this study indicate that PFDA inhibits hepatic glucose transport. Percent hepatic glucose extraction is 1.8-fold greater in controls than in PFDA-treated rats. No significant difference in lactate dehydrogenase levels was observed in the liver perfusate from PFDA-treated and control rats. This suggests that the difference in percent glucose extraction between PFDA-treated and control groups is specifically due to the PFDA treatment and is not attributed to differences in liver viability between groups. Although the exact mechanism for this inhibition in hepatic glucose transport is not known, it is hypothesized that PFDA may have a major impact on membrane structure/function which, in turn, may alter glucose transport.

Animals↗
PubMed1999

Nandrolone decanoate is a good alternative for the treatment of anemia in elderly male patients on hemodialysis.

OBJECTIVE: To assess the efficiency of nandrolone decanoate (ND) in the control of anemia in elderly male patients on hemodialysis (HD), and to determine its influence on nutritional parameters. DESIGN: A prospective 6-month study with randomization of patients on recombinant human erythropoietin (rHuEPO) therapy into two groups. Group A: rHuEPO was stopped before starting treatment with ND. Group E: rHuEPO was continued. SETTING: Renal unit, tertiary-care center. PATIENTS: 14 male patients in Group A and 19 patients, 12 males and 7 females, in Group E. INTERVENTIONS: In Group A rHuEPO was stopped and ND 200 mg/I.M. weekly was given over six months. RESULTS: The increase in hemoglobin and hematocrit levels was progressive with ND, and significant differences (p < 0.003) were evident after six months (9.6 +/- 1.0 vs 11.0 +/- 1.4 and 28.9 +/- 4.7 vs 33.0 +/- 4.7, respectively), which remained unmodified in Group E. Group A showed a significant increase in serum creatinine, total protein, transferrin and anthropometric parameters. These parameters remained stable and even presented a tendency to decrease in Group E. There was a significant rise in the concentration of triglycerides and a significant decrease in both HDL-cholesterol and apolipoprotein A-1 in Group A. However, lipoprotein (a) decreased significantly. No significant changes were detected in Group E. CONCLUSIONS: The use of ND would allow us an acceptable treatment of anemia as well as a better nutritional condition in elderly male patients on dialysis.

Aged↗
PubMed1994

Decanoic acid induced enhancement of rectal absorption of hydrophilic compounds in rats.

The enhancing effect of decanoic acid (C10) on the rectal absorption of phenolsulfonphtalein (PSP) was analyzed with a pharmacokinetic model. The transfer index of PSP from the rectal lumen to the epithelial layer in the presence of C10 was proportional to the product of the C10 disappearance rate from the rectal lumen and its calcium ion sequestration capacity. The enhancement of rectal PSP absorption by different doses of C10 was also predictable by using a permeability index, Pa, of PSP, which was defined as a proportionality constant relating transfer index and the product value described above. The Pa values of various hydrophilic compounds with different molecular weights were also estimated from their rectal bioavailability in the presence of C10. A linear relationship was observed between Pa values and reciprocal values of the square root of individual molecular weight. These findings suggest that the Pa index is related to the permeant's diffusion coefficient through paracellular aqueous openings formed by C10.

Animals↗
PubMed2000

Synchronized release of sulpiride and sodium decanoate from HPMC matrices: a rational approach to enhance sulpiride absorption in the rat intestine.

PURPOSE: (a) To improve the absorption of sulpiride (SP) through the intestinal wall by incorporating it together with sodium decanoate (SD) into erodible matrices, designed to synchronize the release of SP and SD over different periods of time; (b) to test, in vivo the hypothesis that this simultaneous release increases SP absorption from the intestinal lumen. METHODS: Matrix tablets, possessing different erosion rates, were prepared by changing the ratios between SD and hydroxypropyl methylcellulose (HPMC). The amounts of HPMC varied from 2.5% to 17% w/w. Double layer tablets, containing similar amounts of SP, SD, and HPMC were used as nonsynchronous controls. The erosion kinetics of the tablets was assessed gravimetrically in vitro in USP basket dissolution apparatus and in vivo in the intestine of the anesthetized rat after intra-intestinal administration. SP absorption was studied after intra-intestinal administration of the different kinds of tablets to anesthetized rats, by monitoring SP blood levels. SP and SD levels in the withdrawn samples from the dissolution systems and blood were analyzed by HPLC. RESULTS: The controlled erosion of the tablets resulted in equal release rates of SP and SD during the initial linear phase of the process. This synchronized release lasted over different time periods depending on the relative amount of HPMC in the formulations (from 1 hour to 4 hours for 2.5 and 17 % w/w of HPMC, respectively). The synchronous matrices increased SP bioavailability after intra-intestinal administration. The increase varied from 1.4 to 2.3-fold for the slow and the fast release formulations, respectively (compared with the nonsynchronous, SD containing control formulations), indicating the ability to control both erosion rate and length of intestinal segment in which absorption is taking place. CONCLUSIONS: SP bioavailability after intestinal administration can be improved only if SP is released together with SD along the entire intestinal route. This can be accomplished by the design of synchronous matrices capable of concomitant release of SP and SD despite the differences in their water solubility. The ability to manipulate and control the duration of the synchronous phase of the matrices makes it possible for SP to be absorbed at different parts of the intestine.

Animals↗
PubMed1981

Effects of nandrolone decanoate on the toxicity and anti-tumour action of CCNU and FU in murine tumours.

Pre-treatment with the anabolic steroid nandrolone decanoate (ND) increases the LD50 of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 5-Fluorouracil (FU) in NMRI mice. Administration of ND did not affect the anti-tumour action of CCNU against a transplantable mouse adenocarcinoma of the colon (MAC 13) or the anti-tumour action of FU against MAC 26. In both tumour lines ND had no significant effect on tumour growth. These data suggest that an increase in the anti-tumour selectivity of these agents may be produced by pre-treatment with ND.

Adenocarcinoma↗
PubMed2001

The anabolic-androgenic steroid nandrolone decanoate affects the density of dopamine receptors in the male rat brain.

In recent years a male group of anabolic-androgenic steroid misusers has been identified to share socio-demographic and personality related background factors with misusers of psychotropic substances, as well as being involved in habits of multiple drug use. The present study aimed to assess whether anabolic-androgenic steroids (AAS) would affect the density of the dopamine receptors in areas implicated in reward and behaviour in the male rat brain. The effects of 2 weeks of treatment with i.m. injections of nandrolone decanoate (15 mg/kg/day) on the expression of the D(1)-like and D(2)-like receptors were evaluated by autoradiography. Specific binding of D(1)-like receptors was significantly down regulated in the caudate putamen, the nucleus accumbens core and shell. D(2)-like receptor densities were down regulated in the nucleus accumbens shell, but up regulated in the caudate putamen, the nucleus accumbens core and the ventral tegmental area. These results are compatible with nandrolone induced neuroadaptive alterations in dopamine circuits associated with motor functions and behavioural paradigms known to be affected following AAS misuse.

Anabolic Agents↗
PubMed2001

A comparison of megestrol acetate, nandrolone decanoate and dietary counselling for HIV associated weight loss.

This randomized, prospective study compared three treatments, nandrolone decanoate (ND), megestrol acetate (MA) or dietary counselling, for managing human immunodeficiency syndrome (HIV) associated weight loss. It was centred on a Tertiary referral hospital, Sydney, Australia. Fifteen patients were randomized to receive ND (100 mg/fortnight), or MA (400 mg/day) or dietary counselling for 12 weeks. Those patients randomized to dietary counselling were further randomized to receive nandrolone or megestrol after completing the dietary counselling arm. Weight, fat free mass (FFM), percentage body fat mass (FM), dietary intake and appetite were assessed before commencing and at the completion of each treatment arm. Weight increased significantly in all treatment arms (dietary counselling 1.13 kg +/- 0.36, nandrolone 4.01 kg +/- 1.68, megestrol 10.20 kg +/- 4.51, p < 0.05 paired t-test). FFM increased significantly in patients receiving ND (3.54 +/- 1.98 kg, p=0.001) and those receiving MA (2.76 +/- 0.55 kg, p=0.002), whereas the change in those receiving dietary counselling alone was not significant. Percentage body fat mass increased significantly only in those receiving MA (7.77 +/- 4.85%, p=0.049). The change in weight and percentage body fat mass was significantly greater in those receiving MA than the other two treatment arms. The increase in FFM was significantly greater in both the nandrolone and megestrol arms than the dietary counselling arm. It was concluded that ND and MA both resulted in an increase in FFM greater than dietary counselling alone. Megestrol produced a significantly greater increase in weight, percentage fat mass, intake and appetite than did the other two treatment arms, suggesting it may be the preferred agent, particularly in a palliative care setting in which weight, appetite and intake increase are desirable without regard to the composition of the body. The long-term use of these agents in people with HIV should be reviewed in the context of improved survival on highly active antiretroviral therapy regimens.

Adult↗
PubMed1985

Thyroid, bradycardic and hypothermic effects of perfluoro-n-decanoic acid in rats.

A single ip injection of perfluoro-n-decanoic acid (PFDA) to male Wistar rats resulted in an initially rapid, then gradual decrease in food consumption and a parallel loss of body weight. Body temperatures and resting heart rates were significantly depressed by PFDA treatment. As early as 12 h following a single dose of PFDA, serum thyroxine (T4) levels were significantly reduced and remained depressed throughout the 8 day study. Serum triiodothyronine (T3) was reduced by 35% 12 h following PFDA treatment and remained at that level throughout the study. These preliminary data suggest that an action on the thyroid axis may be an early primary response to PFDA and that some of the observed subsequent effects may in part be secondary to the change in thyroid hormone levels.

Animals↗
PubMed1988

Effect of thyroxine supplementation on the response to perfluoro-n-decanoic acid (PFDA) in rats.

The effects of thyroxine (T4) supplementation on perfluoro-n-decanoic acid- (PFDA) induced decreases in food consumption, body weight, and body temperature were examined. A dose-response study was carried out with 50-, 100-, 200-, or 250-micrograms/kg ip doses of T4 for 7 d prior to PFDA administration, and daily dosing with T4 was continued for an additional 30 d. From this study a T4 dose of 200 micrograms/kg was chosen, and subsequent experiments were conducted with this dose. Supplementation with T4 at 200 micrograms/kg daily alleviated the hypophagia but not the severe weight loss and hypothermia produced by PFDA treatment. Our results suggest that some component of the thyroid axis plays a role in feeding behavior. In addition, the PFDA-induced wasting syndrome and hypothermia appear to be unrelated to changes in serum thyroid hormones. The unexpected observation that severe weight loss occurred in the presence of essentially normal food intake suggests that PFDA alters basic cellular metabolic processes.

Animals↗
PubMed1975

Electron microscope autoradiographic study of intestinal absorption of decanoic and octanoic acids in the rat.

Intestinal absorption of [3H]octanoic acid and [3H]decanoic acid was investigated in the rat by electron microscope autoradiography. The common duct (bile and pancreatic common duct) of the rats was diverted and a loop of the duodenum was cannulated 24 h later. The lipid mixture to be investigated was introduced into each experimental loop, and after 15 min or less the loop was removed. One part of each loop was used to determine the distribution of radioactivity in different lipid fractions, and an autoradiographic study was performed on the other part of the loop. Radioactivity distribution studies confirmed that medium chain fatty acids are absorbed in their nonesterified form and established that these fatty acids are absorbed much more rapidly than oleic acid. Autoradiographic studies indicated that the medium chain fatty acids are taken up in a molecular or aggregate molecular form, leave the epithelial cells by way of the lateral plasma membrane, and are next found in the blood capillaries. Our results suggest that the Golgi complex does not play an important role in the absorption of unesterified fatty acids.

Animals↗