Voluntary oral dosing for precise experimental compound delivery in adult rats

2021 ◽  
pp. 002367722110169
Author(s):  
Kyle C Chesler ◽  
Cara T Motz ◽  
Katie L Bales ◽  
Rachael A Allen ◽  
Harrison K Vo ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Adult Male ◽  
High Performance ◽  
Male Rats ◽  
Preclinical Research ◽  
Adult Rats ◽  
Drug Dosing ◽  
Oral Dosing ◽  
Drug Studies ◽  
Delivery Efficiency

Preclinical drug studies routinely administer experimental compounds to animal models with the goal of minimizing potential adverse events from the procedure. In this study, we assessed the ability to train adult male Long Evans rats to accept daily voluntarily syringe feedings of l-3,4-dihydroxyphenylalanine (L-DOPA) compared to intraperitoneal (IP) injections. Rats were trained to become familiar with the syringe and then fed a training solution that did not contain the experimental compound. If the rat was compliant during the training phase, the dilution of training solution was continuously decreased and replaced with the experimental solution. Voluntary oral dosing compliance was recorded and quantified throughout the study. To assess drug activity within the drug-targeted tissues, the striatum and retina were collected and analyzed for L-DOPA, dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels by high performance liquid chromatography (HPLC). Drug delivery efficiency by oral dosing was directly compared to IP injection by collecting plasma and analyzing L-DOPA levels with HPLC. Adult male rats had high compliance for voluntary oral dosing. HPLC showed that oral administration of the compound at the same dose as IP injection yielded significantly lower plasma levels, and that higher oral L-DOPA doses yield higher plasma L-DOPA content. This study describes detailed methodology to train adult rats to syringe feed experimental compounds and provides important preclinical research on drug dosing and drug delivery to the striatum and retina.

scholarly journals Effects of treadmill with different intensities on bone quality and muscle properties in adult rats

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Zhehao Liu ◽  
Jiazi Gao ◽  
He Gong
Keyword(s):  
Cortical Bone ◽  
Soleus Muscle ◽  
Adult Male ◽  
Biomechanical Properties ◽  
Treadmill Running ◽  
Male Rats ◽  
Bending Test ◽  
Long Bone ◽  
Nanoindentation Test ◽  
Adult Rats

Abstract Background Bone is a dynamically hierarchical material that can be divided into length scales of several orders of magnitude. Exercise can cause bone deformation, which in turn affects bone mass and structure. This study aimed to study the effects of treadmill running with different intensities on the long bone integrity and muscle biomechanical properties of adult male rats. Methods Forty-eight 5-month-old male SD rats were randomly divided into 4 groups: i.e., sedentary group (SED), exercise with speed of 12 m/min group (EX12), 16 m/min group (EX16), and 20 m/min group (EX20). The exercise was carried out for 30 min every day, 5 days a week for 4 weeks. The femurs were examined using three-point bending test, microcomputer tomography scanning and nanoindentation test; the soleus muscle was dissected for tensile test; ALP and TRACP concentrations were measured by serum analysis. Results The failure load was significantly increased by the EX12 group, whereas the elastic modulus was not significantly changed. The microstructure and mineral densities of the trabecular and cortical bone were significantly improved by the EX12 group. The mechanical properties of the soleus muscle were significantly increased by treadmill exercise. Bone formation showed significant increase by the EX12 group. Statistically higher nanomechanical properties of cortical bone were detected in the EX12 group. Conclusion The speed of 12 m/min resulted in significant changes in the microstructure and biomechanical properties of bone; besides, it significantly increased the ultimate load of the soleus muscle. The different intensities of treadmill running in this study provide an experimental basis for the selection of exercise intensity for adult male rats.

EFFECTS OF FOLLICLE-STIMULATING HORMONE AND LUTEINIZING HORMONE ON PLASMA TESTOSTERONE LEVELS IN HYPOPHYSECTOMIZED AND IN INTACT IMMATURE AND ADULT MALE RATS

1974 ◽  
Vol 61 (2) ◽  
pp. 193-198 ◽  
Author(s):  
S. EL SAFOURY ◽  
A. BARTKE
Keyword(s):  
Luteinizing Hormone ◽  
Adult Male ◽  
Follicle Stimulating Hormone ◽  
Seminal Vesicles ◽  
Male Rats ◽  
Plasma Testosterone ◽  
Adult Rats ◽  
Testosterone Levels ◽  
Hypophysectomized Rats ◽  
Stimulating Hormone

SUMMARY The effects of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on plasma testosterone levels were examined in hypophysectomized and in intact immature and adult male rats. The animals were injected with saline, LH, FSH, or both gonadotrophins twice daily for 3·5 days and were killed 3 h after the last injection. Plasma testosterone levels were measured by radioimmunoassay. In immature hypophysectomized rats, plasma testosterone levels were not changed by treatment with LH, FSH or LH plus FSH. The weight of the testes and of the seminal vesicles was increased only in animals injected with both LH and FSH. In adult hypophysectomized rats, LH caused the expected increase in plasma testosterone levels, while FSH injected alone had no effect. Plasma testosterone levels in rats treated with 5 μg LH and 20 μg FSH were significantly greater than those in animals given 5 μg LH alone. However, the same dose of FSH did not potentiate the action of 25 μg LH on plasma testosterone levels. In adult hypophysectomized rats the weight of testes was not affected by any of the treatments. The weight of the seminal vesicles was increased by the higher dose of LH and addition of FSH caused no further increase. In intact immature and adult rats plasma testosterone levels and the weight of testes were not changed by any of the treatments. Seminal vesicle weight was increased only in adult rats treated with the higher dose of LH together with FSH. The results demonstrate that FSH potentiates the action of low doses of LH on plasma testosterone levels in adult hypophysectomized rats and suggest that FSH may be involved in the regulation of androgen secretion by the rat testis.

Urethral plug-a new secondary male sex characteristic in rat and other rodents

1982 ◽  
Vol 16 (2) ◽  
pp. 151-155 ◽  
Author(s):  
Ivo Kunstýř ◽  
Werner Küpper ◽  
Herwig Weisser ◽  
Susanne Naumann ◽  
Claus Messow
Keyword(s):  
Amino Acid ◽  
Amino Acid Composition ◽  
Adult Male ◽  
Seminal Vesicles ◽  
Male Rats ◽  
Average Weight ◽  
Adult Rats ◽  
Vaginal Plug ◽  
Male Sex ◽  
Proximal Urethra

The plug is an eosinophilic mass, partly homogenous and partly porous, filling the proximal urethra in rats and occasionally extending into the bladder. Its average weight in 131 adult rats was 0·063 g. These plugs are normally present in the urethra of adult male rats, and this seems to be the case for all laboratory Muridae and Cavidae. The absence of a plug in an adult male may be a sign of abnormality associated with failing health. There is an interesting similarity between the amino acid composition of the content of seminal vesicles, that of the urethral plug, and that of the copulatory vaginal plug in female rodents.

scholarly journals Gender Differences in the Effect of Prenatal Methamphetamine Exposure and Challenge Dose of Other Drugs on Behavior of Adult Rats

2013 ◽  
pp. S99-S108 ◽  
Author(s):  
R. ŠLAMBEROVÁ ◽  
E. MACÚCHOVÁ ◽  
K. NOHEJLOVÁ-DEYKUN ◽  
B. SCHUTOVÁ ◽  
L. HRUBÁ ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Adult Male ◽  
Gonadal Hormones ◽  
Female Rats ◽  
Male Rats ◽  
Prenatally Exposed ◽  
Challenge Dose ◽  
Adult Rats ◽  
Male And Female ◽  
Male And Female Rats

The aim of the present study was to compare the response to acute application of several drugs in adult male and female rats prenatally exposed to methamphetamine (MA). Spontaneous locomotor activity and exploratory behavior of adult male and female rats prenatally exposed to MA (5 mg/kg) or saline were tested in a Laboras apparatus (Metris B.V., Netherlands) for 1 h. Challenge dose of the examined drug [amphetamine – 5 mg/kg; cocaine – 5mg/kg; MDMA (3,4-methylenedioxymethamphetamine) – 5 mg/kg; morphine – 5 mg/kg; THC (delta9-tetrahydrocannabinol) – 2 mg/kg] or saline was injected prior to testing. Our data demonstrate that prenatal MA exposure did not affect behavior in male rats with cocaine or morphine treatment, but increased locomotion and exploration in females. Application of amphetamine and MDMA in adulthood increased activity in both sexes, while cocaine and THC only in female rats. Morphine, on the other hand, decreased the activity in the Laboras test in both sexes. As far as sex and estrous cycle is concerned, the present study shows that males were generally less active than females and also females in proestrus-estrus phase of the estrous cycle were more active than females in diestrus. In conclusion, the present study shows that the prenatal MA exposure does not induce general sensitization but affects the sensitivity to drugs dependently to mechanism of drug action and with respect to gonadal hormones.

Reproductive toxicity and tissue concentrations of 3,3',4,4'-tetrachlorobiphenyl (PCB 77) in male adult rats

1998 ◽  
Vol 17 (3) ◽  
pp. 151-156 ◽  
Author(s):  
A S Faqi ◽  
P R Dalsenter ◽  
W Mathar ◽  
B Heinrich-Hirsch ◽  
I Chahoud
Keyword(s):  
Adult Male ◽  
Weight Control ◽  
Reproductive Toxicity ◽  
Serum Testosterone ◽  
Male Rats ◽  
Testis Weight ◽  
Adult Rats ◽  
Male Adult ◽  
Reproductive Effects ◽  
Investigation Period

1 The aim of this study was to ascertain the reproductive effects of PCB 77 on adult male rats and to determine its concentration in the liver and testis. Adult male rats (n=15/group) were treated subcutaneously with a singledoseof18 mg/kgbw(PC18)orwith60 mg/kg bw (PC60). The substance was dissolved in a 10 ml volume of peanut oil/kg. Control rats received the same volume of the vehicle. The reproductive effects as well as the concentration of PCB 77 in the liver and testis were investigated 1, 4 and 8 weeks after treatment. 2 In both groups, the daily sperm production (DSP; 6106) remained permanently reduced in the PC18 as well as in the PC60 groups throughout the entire investigation period (DSP week 8: control: 31+7; PC18: 22+5; PC60: 20+7). The sperm number (6106) per cauda epididymis was affected only at the 1st and 4th week after treatment (control week 1: 211+67; PC18 week 1: 135+62; PC60 week 1: 142+49). Moreover, a significant increase in the percentage of abnormal sperm was observed 4 weeks following treatment in the PC18 and PC60 groups and 8 weeks after treatment in the PC60 group. Abnormal tails were the most frequent changes observed. 3 The relative testicular and prostata weights (g) were slightly increased in the PC60 group at the 1st and 4th week following treatment (testis weight: control/I: 0.46+0.02; PC60/I: 0.51+0.03). 4 The serum testosterone concentrations and effects on testis morphology were not reported. 5 The maximum concentration of PCB 77 was detected in the liver and testis 1 week after treatment. The concentration declined 4 weeks after treatment in both organs, but still a significant amount of PCB 77 was detectable in the liver as well as in the testis 8 weeks after treatment. 6 The results demonstrate that PCB 77 affects sperm variables when applied to adult rats and that the elimination of PCB 77 in the testis parallels that of the liver.

scholarly journals Effect of tamsulosin on testis histopathology and serum hormones in adult rats: Experimental study

2020 ◽  
Author(s):  
Yegane Kohestani ◽  
Bentolhoda Kohestani ◽  
Zahra Shirmohamadi ◽  
Masoumeh Faghani
Keyword(s):  
Experimental Study ◽  
Adult Male ◽  
Clinical Symptoms ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Control Group ◽  
Adult Rats ◽  
Serum Hormones ◽  
Alpha Adrenergic Receptors ◽  
Testicular Weight

Background: Tamsulosin is an inhibitory factor of alpha-adrenergic receptors that is used for relieving of the clinical symptoms and management of acute urinary retention. Objective: The aim of this study was to evaluate the effects of tamsulosin on the endocrine axis and testicular tissue in adult male rats. Materials and Methods: In this experimental study, 30 adult male Wistar rats (weighing 250-300 gr) were divided into three groups: 1) control (received distilled water), 2) experimental 1 (received 0.2 mg/kg/day tamsulosin) and 3) experimental 2 (received 0.4 mg/kg/day tamsulosin) through oral gavage for 28 days. Serum hormones level and testicular histopathology were evaluated at the end of the experiment. Results: In this study, the testicular weight decreased significantly in the experimental groups compared to the control group. A significant decrease was seen in testicular weight (p = 0.004) and the number of Leydig cells in tamsulosin-treated groups (p = 0.012). Tamsulosin improved the hormone profile in experimental groups. Also, higher dose of tamsulosin significantly changed the number of Leydig, spermatogonia cells, the thickness of germinal layer, and the diameter of the seminiferous tubules. Conclusion: Results showed that using tamsulosin, possibly reduces the testosterone concentration through adrenergic axis system and in turn has destructive effects on proliferative activity of germ cells. Key words: Tamsulosin, Seminiferous tubules, Histopathology, Rat, Testis.

ON RAT SERUM LIPASE

1952 ◽  
Vol 30 (1) ◽  
pp. 26-35
Author(s):  
Jules Tuba ◽  
Jack D. Taylor
Keyword(s):  
Food Consumption ◽  
Adult Male ◽  
Elevated Serum ◽  
Male Rats ◽  
Normal Male ◽  
Adult Rats ◽  
Rat Serum ◽  
Serum Lipase ◽  
Fat Consumption ◽  
Daily Food

There is no correlation in either weanling or adult normal male rats between daily food consumption of a stock laboratory diet and serum tributyrinase activity. Limiting the food intake of adult male rats has no statistically significant effects on serum tributyrinase. The abnormally elevated serum tributyrinase levels of alloxan diabetic adult male rats may be accounted for on the basis of increased food consumption. Weanling and adult male animals maintained on synthetic diets containing from 5 to 60% fat show a correlation between serum tributyrinase concentration and daily fat consumption. In the case of adult rats increased fat ingestion is accompanied by increased enzyme activity. However, with weanling rats increased fat consumption results in lowered tributyrinase concentrations and retarded growth. The results with growing animals are attributed to the decreased intake of food, and the corresponding decrease in protein consumption, which accompanies the increase in dietary fat concentration. Replacement of the synthetic diets by the stock laboratory diet is followed by altered tributyrinase levels in both weanling and adult animals.

scholarly journals Do Prenatally Methamphetamine-Exposed Adult Male Rats Display General Predisposition to Drug Abuse in the Conditioned Place Preference Test?

2012 ◽  
pp. S129-S138
Author(s):  
R. ŠLAMBEROVÁ ◽  
M. POMETLOVÁ ◽  
B. SCHUTOVÁ ◽  
L. HRUBÁ ◽  
E. MACÚCHOVÁ ◽  
...  
Keyword(s):  
Drug Abuse ◽  
Pregnant Women ◽  
Conditioned Place Preference ◽  
Adult Male ◽  
Place Preference ◽  
Male Rats ◽  
Self Administration ◽  
Adult Rats ◽  
Drug Seeking ◽  
Seeking Behavior

Drug abuse of pregnant women is a growing problem. The effect of prenatal drug exposure may have devastating effect on development of the offsprings that may be long-term or even permanent. One of the most common drug abused by pregnant women is methamphetamine (MA), which is also the most frequently abused illicit drug in the Czech Republic. Our previous studies demonstrated that prenatal MA exposure alters behavior, cognition, pain and seizures in adult rats in sex-specific manner. Our most recent studies demonstrate that prenatal MA exposure makes adult rats more sensitive to acute injection of the same or related drugs than their controls. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the Conditioned place preference (CPP). Adult male rats were divided to: prenatally MA-exposed (5 mg/kg daily for the entire prenatal period), prenatally saline-exposed (1 ml/kg of physiological saline) and controls (without maternal injections). The following drugs were used in the CPP test in adulthood: MA (5 mg/kg), amphetamine (5 mg/kg), cocaine (5 and 10 mg/kg), morphine (5 mg/kg), MDMA (5 mg/kg) and THC (2 mg/kg). Our data demonstrated that prenatally MA-exposed rats displayed higher amphetamine-seeking behavior than both controls. MA as well as morphine induced drug-seeking behavior of adult male rats, however this effect did not differ based on the prenatal MA exposure. In contrast, prenatal MA exposure induced rather tolerance to cocaine than sensitization after the conditioning in the CPP. MDMA and THC did not induce significant effects. Even though the present data did not fully confirmed our hypotheses, future studies are planned to test the drug-seeking behavior also in self-administration test.

scholarly journals Leptin inhibits testosterone secretion from adult rat testis in vitro

1999 ◽  
Vol 161 (2) ◽  
pp. 211-218 ◽  
Author(s):  
M Tena-Sempere ◽  
L Pinilla ◽  
LC Gonzalez ◽  
C Dieguez ◽  
FF Casanueva ◽  
...  
Keyword(s):  
Adult Male ◽  
Reproductive Function ◽  
Serum Testosterone ◽  
Testicular Tissue ◽  
Male Rats ◽  
Adult Males ◽  
Adult Rats ◽  
Adult Rat ◽  
Testosterone Secretion

Leptin, the product of the ob gene, has emerged recently as a pivotal signal in the regulation of fertility. Although the actions of leptin in the control of reproductive function are thought to be exerted mainly at the hypothalamic level, the potential direct effects of leptin at the pituitary and gonadal level have been poorly characterised. In the present study, we first assessed the ability of leptin to regulate testicular testosterone secretion in vitro. Secondly, we aimed to evaluate whether leptin can modulate basal gonadotrophin and prolactin (PRL) release by incubated hemi-pituitaries from fasted male rats. To attain the first goal, testicular slices from prepubertal and adult rats were incubated with increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Assuming that in vitro testicular responsiveness to leptin may be dependent on the background leptin levels, testicular tissue from both food-deprived and normally-fed animals was used. Furthermore, leptin modulation of stimulated testosterone secretion was evaluated by incubation of testicular samples with different doses of leptin in the presence of 10 IU human chorionic gonadotrophin (hCG). In addition, analysis of leptin actions on pituitary function was carried out using hemi-pituitaries from fasted adult male rats incubated in the presence of increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Serum testosterone levels, and basal and hCG-stimulated testosterone secretion by incubated testicular tissue were significantly decreased by fasting in prepubertal and adult male rats. However, a significant reduction in circulating LH levels was only evident in adult fasted rats. Doses of 10(-9)-10(-7) M leptin had no effect on basal or hCG-stimulated testosterone secretion by testes from prepubertal rats, regardless of the nutritional state of the donor animal. In contrast, leptin significantly decreased basal and hCG-induced testosterone secretion by testes from fasted and fed adult rats. In addition, 10(-9) M leptin inhibited LH and FSH secretion by incubated hemi-pituitaries from fasted adult males, whereas, at all doses tested, it was ineffective in modulating PRL release. Our results show that leptin, depending on the state of sexual maturation, is able to inhibit testosterone secretion acting at the testicular level. Furthermore, the present data suggest that the actions of leptin on the reproductive system are complex and are probably carried out at different levels of the hypothalamic-pituitary-gonadal axis.

ANDROGEN-DEPENDENT SYNTHESIS OF α2u GLOBULIN IN THE RAT: ROLE OF THE PITUITARY GLAND

1973 ◽  
Vol 56 (2) ◽  
pp. 295-301 ◽  
Author(s):  
A. K. ROY
Keyword(s):  
Growth Hormone ◽  
Pituitary Gland ◽  
Adult Male ◽  
Synergistic Effects ◽  
Pituitary Hormones ◽  
Male Rats ◽  
Adult Rats ◽  
Simultaneous Treatment ◽  
Complete Reversal

SUMMARY Hypophysectomy completely abolished the androgen-dependent synthesis of α2u globulin in adult rats. Experiments with adrenalectomized and thyroidectomized adult male rats showed that these endocrine ablations also reduced the daily urinary output of α2u globulin to about 10% or less than those of the pre-operative values. The effects of adrenalectomy and thyroidectomy on α2u output could be reversed to normal with the supplementation of corticosterone and thyroxine respectively. However, none of the pituitary hormones administered alone or along with testosterone was able to reverse the effect of hypophysectomy. Simultaneous treatment with growth hormone, corticosterone and thyroxine along with testosterone was required for the complete reversal of the effect of hypophysectomy. It is concluded that the androgenic induction of α2u globulin is dependent on the synergistic effects of growth and developmental hormones such as growth hormone, thyroxine and corticosterone.

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