Effects of baclofen on anxiety level, sexual motivation and olfactory perception in male mice with different psycho-emotional statuses

Effects of GABA-B agonist baclofen (1, 2.5, 5 pg/kg, i. p.) on sexual and anxiety reactions and olfactory perception in C57Bl/6J male mice with different psychoemotional statuses (intact, aggressive, submissive) were studied. Baclofen increased time of finding olfactory bait. Baclofen's effects depend from psychoemotional statuses of animals. In intact males, baclofen carries anxiolytic effects and increase of sexual motivation; in submissive males, the drug does not influence on anxiety level, but prevents sexual interest from reduction; in aggressive males, baclofen increases anxiety level, but restores decreased sexual motivation.     

Effects of dehydroepiandrosterone-sulfate on sexual motivation in male mice with different psychoemotional statuses

Effects of dehydroepiandrosterone-sulfate (10, 30 and 100 microg/kg, i.p.) on stability of sexual motivation of C57BL/6J male mice with different psychoemotional statuses were studied. Sexual motivation was assessed for 30 min in the sensory contact setting: a male was exposed to a female at oestrus from behind a perforated transparent partition which prevented physical contact. In the intact males, dehydroepiandrosterone-sulfate injection (10 and 30 microg/kg) 4 hrs before the test had no effect on parameters of sexual motivation. In aggressive males, administration of the dehydroepiandrosterone-sulfate had no effect on the intensity of the initial 10 min phase of sexual motivation but prevented its rapid decrease afterwards. In submissive mice, either dose reduced intensity of the initial phase of behavioral reaction to receptive female; however, tile higher dose prevented motivation from exhaustion, and so interest to the female was persistent, albeit decreased. The highest dose of dehydroepiandrosterone-sulfate had inhibitory effects on stability of the sexual interest in the male mice of all experimental groups.     

Psychotropic effects of glutamic acid diethyl ester in mice

In 1 hour after intraperitoneal injection glutamic acid diethyl ester (GED) in doses 200 and 500 mg/kg decreased locomotor activity and exploratory patterns of mice in "open field" test. GED in doses 100 and 200 mg/kg diminished the immobilization period of animals in forced swimming test, that proves the reversal interaction of glutamatergic and catecholaminergic systems in CNS. Glutamate receptors antagonist--GED in doses 100-200 mg/kg disrupted passive avoidance reaction at 30 min before acquisition and retrieval, therefore glutamate receptors are involved into fixation and retrieval of memory engram.     

Antimutagenic effects on male germ cells of mice

The alkylating agent cyclophosphamide (CPA) and the antioxidant ethoxyquin (EQ) were administered perorally to NMRI mice. The strong clastogenic action of CPA on spermatogonia was diminished by simultaneous doses of EQ. Higher doses of the antioxidant produced greater anticlastogenic action. Furthermore, the action of the mutagen and the antioxidant on the late spermatids and the spermatozoa was observed using the dominant lethal test. The antioxidant had only a weak influence on these postmeiotic stages.     

Genetic effects of radiocarbon in reproductive cells of male mice

The genetic effect of incorporated radiocarbon was studied after single, long-term (33 days) and chronic (6 and 12 months) treatment of male mice (CBA X C57B1) F1 with [14C]glucose. The genetic effect in male germ cells was estimated by 3 tests: DLM frequency in post- and pre-meiotic cells, RT frequency in stem spermatogonia and frequency of abnormal sperm heads. Absorbed doses in the gonads were: 0.22, 0.50 and 1.01 Gy, after a single exposure; 0.74 and 1.47 Gy, after long-term exposures; and 0.006 and 0.031 Gy, after chronic exposure for 6 months; and 0.013 and 0.066 Gy, for 12 months. The results suggest that DLM frequency in post-meiotic cells increased linearly with increasing the dose of 14C single and long-term exposures at a dose of 1.47 Gy only. A chronic treatment with [14C]glucose induced no increase in DLM frequency. RT frequency in stem spermatogonia was statistically significantly higher than the control level after the single and long-term exposure to 14C. A comparison of the results with the results of external single and chronic gamma-irradiation allows the conclusion that the relative genetic efficiency of radiocarbon as compared with that of gamma-rays is about 1.     

Genetic effects of 131I in reproductive cells of male mice

A study was made of the frequencies of dominant lethal mutations (DLM) in pre- and post-meiotic germ cells, reciprocal translocations (RT) in spermatogonia and abnormal sperm heads (ASH) induced by a single intraperitoneal administration of Na131I with an activity of 1.48-740 kBq/g to male mice. The frequency of DLM was shown to increase only when postmeiotic cells were exposed to the radionuclide. The RT frequency increased insignificantly with increases in the dose of 131I. The ASH frequency increased only when maximal doses of 131I were administered. The relative biological efficiency (RBE) of 131I with reference to the indices under study is less than 1.     

Diazepam sensitive mice: differential sensitivity to the depressant and anticonvulsant effects of diazepam

A mouse line was developed by selecting for increased sensitivity to the hypnotic effect of diazepam. These "diazepam sensitive" mice showed a mean duration of loss of righting reflex (LORR) of approximately 150 min at a dose of 20 mg/kg diazepam, this dose failed to induce LORR in the control outbred mice. Rotarod treading times of the diazepam sensitive mice were significantly shorter than that of the control mice over the same dose range indicating that these mice are also more sensitive to the sedative/muscle relaxant effects of diazepam. On the contrary, the ability of diazepam to protect against pentylenetetrazole-induced convulsion was found to be the same in the sensitive and control mice. These observations strongly suggest that the heightened sensitivity to the sedative-hypnotic effects of diazepam in the sensitive mice is unlikely to be due entirely to changes in drug disposition.     

Synergistic effects of germ cell expressed genes on male fertility in mice

Over 200 genes have been shown to be associated with infertility in mouse models. However, knockout mice reveal unexpected functional redundancy of some germ cell expressed genes. Single null mutations in mouse genes encoding four male germ cell proteins, transition protein 2 (Tnp2), proacrosin (Acr), histone H1.1 (H1.1), histone H1t (H1t) and sperm mitochondria-associated cysteine-rich protein (Smcp) have been generated and analysed. Tnp2 is believed to participate in the removal of the nuclear histones and initial condensation of the spermatid nucleus. Proacrosin is an acrosomal protease synthesized as a proenzyme and activated into acrosin during the acrosome reaction. The linker histone subtype H1.1 belongs to the group of main-type histones and is synthesized in somatic tissues as well as in germ cells during the S-phase of the cell cycle. The histone gene Hist1h1t is expressed exclusively in spermatocytes and may have a function in establishing an open chromatin structure for the replacement of histones by transition proteins and protamines. Sperm mitochondria-associated cysteine-rich protein (Smcp) is a major structural element of the mitochondria in the midpiece of the sperm tail. Male mutant mice lacking any of these proteins show no apparent defects in spermatogenesis or fertility. To examine the synergistic effects of these proteins in spermatogenesis and during fertilization four lines of double knockout mice Hist1h1a/Mcsp, Hist1h1t/Mcsp, Tnp2/Mcsp and Acr/Mcsp were established. It was found that even when knockout mice are heterozygous for one allele (-/+) and homozygous for the other allele (-/-), mice were subfertile. Homozygous double knockout mice of all four lines are nearly infertile. However, in the four homozygous double knockout mouse lines, different characteristic abnormalities are prominently manifested: In Hist1h1a-/-/Mcsp-/- the migration of spermatozoa is disturbed in female genital tract, in Hist1h1t-/-/Mcsp-/- spermatozoa show morphological head abnormalities, in Tnp2-/-/Mcsp-/- the motility of sperm is affected, and in Acr-/-/Mcsp-/- the sperm-oocyte interaction is impaired. These findings indicate strongly that male germ cell expressed genes have synergistic effects on male fertility.     

Dynamic pathways of selenium metabolism and excretion in mice under different selenium nutritional statuses

The selenoprotein, cellular glutathione peroxidase (cGPx), has an important role in protecting organisms from oxidative damage through reducing levels of harmful peroxides. The liver and kidney in particular, have important roles in selenium (Se) metabolism and Se is excreted predominantly in urine and feces. In order to characterize the dynamics of these pathways we have measured the time-dependent changes in the quantities of hepatic, renal, urinary, and fecal Se species in mice fed Se-adequate and Se-deficient diets after injection of (82)Se-enriched selenite. Exogenous (82)Se was transformed to cGPx in both the liver and kidney within 1 h after injection and the synthesis of cGPx decreased 1 to 6 h and continued at a constant level from 6 to 72 h after injection. The total amount of Se associated with cGPx in mice fed Se-deficient diets was found to be less than in mice fed Se-adequate diets. This finding indicated that cGPx synthesis was suppressed under Se-deficient conditions and did not recover with selenite injection. Excess Se was associated with selenosugar in liver and transported to the kidney within 1 h after injection, and then excreted in urine and feces within 6 h after injection. Any excess amount of Se was excreted mainly as a selenosugar in urine.     

Gender-related differences in diazepam effects on performance

In order to investigate the possible differences of diazepam effects in the two sexes, two placebo-controlled double-blind studies were conducted on healthy volunteer students. In one study the subjects received diazepam 10 mg alone or combined with 0.5 g/kg of alcohol in a parallel group design; in the other 0.2 mg/kg of diazepam or placebo were given in a cross-over manner. In both trials diazepam impaired the psychomotor skills of women more than men. The difference was similar in tasks measuring cognitive (digit symbol substitution), motor (balance of extraocular muscles) and sensory (critical flicker fusion) performances. Tapping speed was affected to a similar degree in both genders. Diazepam 10 mg did not cause impairment of body balance, a parameter sensitive to alcohol. The combined effect of diazepam and alcohol was of similar magnitude in both sexes in all objective tests. Subjectively the women felt themselves clumsier than did the men. The calming effect was similar in both groups. The results suggest that while the performance of women may be more vulnerable than men to impairment by diazepam they also are aware of it. The difference of effects is of such magnitude that it may cause bias in experiments unless carefully balanced groups are used.     

Marked variation in diazepam sensitivity in Swiss albino mice

Using the righting reflex as the critical level, sleep was measured in Swiss albino mice at a dose of 35 mg/kg diazepam, i.p. Sleep times varied markedly from zero to 120 min with a mean +/- s.d. of 44 +/- 37 (N = 202). The distribution is skewed to the left with a coefficient of skewness of 0.33 +/- 0.17. The sleep times of the two sexes, when analyzed separately, showed similar range, mean and s.d., except that the distribution tended to be more clearly bimodal in males than in females. These animals also exhibited marked variations in their response to either ethanol (4 g/kg) or pentobarbital (45 mg/kg). The diazepam sleep time failed to correlate with the ethanol sleep time. Significant correlation, however, was obtained between diazepam and pentobarbital sleep times. On further analysis with least-squares fit to a straight line, the data yielded a line with a slope of 0.16; thus despite the correlation reaching a significant level, there is no significant difference in the pentobarbital sleep times between mice that have the longest or the shortest diazepam sleep times. By monitoring the plasma and brain levels of diazepam and N-desmethyldiazepam in mice at awakening, it was found that the variations in sleep time cannot be explained by individual differences in drug disposition. The phenomenon is discussed in terms of individual variations in diazepam sensitivity and the possibility of development of tolerance to diazepam almost immediately after diazepam administration.     

Cytogenetic effects of protracted gamma exposures from conception of male mice

In order to gain an overall picture of the genetic effects of an increased level of background radiation it is necessary to study the results of protracted exposures to embryonic and immature germ-cell stages as well as to stages found in the mature organism. For this purpose, litters produced by female mice, kept in a 10 or 20 rad/day ⁶⁰Co-γ-irradiation field, were kept in the same fields from conception until about 60 days later, having absorbed doses of 526 and 1078 rad respectively. Tests on exposed female offspring showed them to be sterile. 8 weeks after removal from the gamma field, mean testis masses of males in the 20 rad/day series were only half normal but those receiving 10 rad/day were little affected. Frequencies of translocations in spermatocytes at diakinesis/metaphase I were only slightly increased in the exposed series, differences not being significant. Estimated rates of translocation induction were around 5 × 10^?6 per rad, about one-third of those found after protracted γ-irradiation of stem-cell spermatogonia in the adult. Embryonic lethality in progeny of other similarly irradiated males (absorbed doses of 560 and 1040 rad), mated 2 months after removal from the radiation fields, was also increased slightly, but not significantly. Results are compared with others on the induction of chromosome aberrations and gene mutations, mainly by acute irradiation, in prenatal and neonatal male mice. It is concluded that early male germ-cell stages generally show a reduced genetic radiosensitivity after both acute and chronic exposures.     

Hormone levels of male African striped mice change as they switch between alternative reproductive tactics

Alternative reproductive tactics occur when individuals of the same species follow alternative ways to maximize reproductive success. Often younger and smaller males follow tactics that result in lower fitness than that of dominant larger males. The relative plasticity hypothesis predicts that hormone levels change as males change tactics, but direct tests of this hypothesis are missing. It has been demonstrated in a number of studies that males following different tactics also differ in hormone levels (unpaired data), but not that individual males change their hormone levels as they change tactic (paired data). We compared hormone levels in the same individuals before and after they changed their tactic, using field samples collected over a period of 6 years. We studied male striped mice (Rhabdomys pumilio) following three alternative reproductive tactics: 1. alloparental philopatric males; 2. solitary roaming males, and 3. group-living dominant breeders. Testosterone levels increased and corticosterone levels decreased when philopatric males became roamers or breeders. The increase in testosterone levels tended to be higher in philopatric males that became roamers than in philopatric males that became breeders. Testosterone levels decreased when roamers became breeders. Prolactin levels increased when males of any other tactic became breeders. Thus, males significantly changed their hormone profiles as they changed tactics. These results are in agreement with the hypothesis that changes in hormone levels are associated with the switch from one alternative reproductive tactic to another.     

Electroencephalographic changes with age in male mice.

Electroencephalographic (EEG) changes, as measured by the awake state, slow-wave sleep (SWS), rapid-eye movement (REM) patterns and ratio of REM/total sleep, were recorded in aging male mice of DBA/2J and C57BL/6J strains. Results indicate that there is a significant increase in the awake state accompanied by significant decrease in SWS with advancing age for both strains, although these changes appear more pronounced in DBA/2J mice than C57BL/6J mice. Of considerable significance is the finding that REM sleep is absent in mice of DBA/2J strain at 23.5 months of age. Based on these findings, the conclusion was reached that strain DBA/2J ages significantly faster than C57BL/6J. The difference in aging between the two strains emphasizes the need for additional studies dealing with genetic aspects of aging.     

Teratogenic effects of diazepam in the hamster.

Pregnant hamsters were treated with different doses of oral and intravenous diazepam during the period of organogenesis. Teratogenic effects of diazepam were observed following oral treatment on days 8 and 10 and following intravenous treatment on day 11 of gestation. Types of malformations included cleft palate, exencephaly, limb anomalies, and hemorrhage. A dose-effect relationship was not observed. Comparison with reported literature seems to indicate that diazepam may be a mild teratogen in some species.