DRD1 5'UTR variation, sex and early infant stress influence ethanol consumption in rhesus macaques

The mesolimbic dopamine system plays an important role in mediating a variety of behaviors and is involved in mediating the reinforcing effects of ethanol. Genes encoding dopamine receptor subtypes are thus good candidate loci for understanding the genetic etiologies of susceptibility to alcohol dependence and its antecedent behavioral phenotypes. We tested whether variation in DRD1 influences alcohol consumption in rhesus macaques and whether its influence is mediated by sex and early rearing experience. We genotyped a single nucleotide polymorphism (−111 G/T) in the 5'UTR of DRD1 in 96 subjects raised with their mothers until 6 months of age ( n = 43) or in peer-only groups ( n = 53). As young adults they underwent a 7-week voluntary ethanol consumption experiment. anova revealed a significant main effect of sex ( F _1,95 = 6.3, P = 0.014) and an interaction between genotype, sex and rearing on ethanol consumption ( F _7,95 = 4.63, P = 0.0002). Maternally deprived males heterozygous for the T allele consumed significantly more ethanol ( P > t ≤ 0.0001) than the other subgroups. Maternal deprivation can produce individuals that are anxious and impulsive, both of which are known risk factors for alcohol dependence. Our work demonstrates a potential role for the dopamine D1 receptor gene in modulating alcohol consumption, especially in the context of early environmental stress.     

Effects of sex and estrous cycle on the brain and plasma arginine metabolic profile in rats

l-arginine is a versatile amino acid with a number of bioactive metabolites. Increasing evidence implicates altered arginine metabolism in the aging and neurodegenerative processes. The present study, for the first time, determined the effects of sex and estrous cycle on the brain and blood (plasma) arginine metabolic profile in naïve rats. Female rats displayed significantly lower levels of l-arginine in the frontal cortex and three sub-regions of the hippocampus when compared to male rats. Moreover, female rats had significantly higher levels of l-arginine and γ-aminobutyric acid, but lower levels of l-ornithine, agmatine and putrescine, in plasma relative to male rats. The observed sex difference in brain l-arginine appeared to be independent of the enzymes involved in its metabolism, de novo synthesis and blood-to-brain transport (cationic acid transporter 1 protein expression at least), as well as circulating l-arginine. While the estrous cycle did not affect l-arginine and its metabolites in the brain, there were estrous cycle phase-dependent changes in plasma l-arginine. These findings demonstrate the sex difference in brain l-arginine in the estrous cycle-independent manner. Since peripheral blood has been increasingly used to identify biomarkers of brain pathology, the influences of sex and estrous cycle on blood arginine metabolic profile need attention when experimental research involves female rodents.

     

The anorectic effect of fenfluramine is influenced by sex and stage of the estrous cycle in rats

The controls of food intake differ in male and female rats. Daily food intake is typically greater in male rats, relative to female rats, and a decrease in food intake, coincident with the estrous stage of the ovarian reproductive cycle, is well documented in female rats. This estrous-related decrease in food intake has been attributed to a transient increase in the female rat's sensitivity to satiety signals generated during feeding bouts. Here, we investigated whether sex or stage of the estrous cycle modulate the satiety signal generated by fenfluramine, a potent serotonin (5-HT) releasing agent. To examine this hypothesis, food intake was monitored in male, diestrous female, and estrous female rats after intraperitoneal injections of 0, 0.25, and 1.0 mg/kg D-fenfluramine. The lower dose of fenfluramine decreased food intake only in diestrous and estrous females, suggesting that the minimally effective anorectic dose of fenfluramine is lower in female rats, relative to male rats. Although the larger dose of fenfluramine decreased food intake in both sexes, the duration of anorexia was greater in diestrous and estrous female rats, relative to male rats. Moreover, the magnitude of the anorectic effect of the larger dose of fenfluramine was greatest in estrous rats, intermediate in diestrous rats, and least in male rats. Thus our findings indicate that the anorectic effect of fenfluramine is modulated by gonadal hormone status.     

The influence of chronic ethanol consumption on the distribution of thiopental in rats.

Ethanol was administered chronically for 14 days to male Sprague-Dawley rats. Day 15 was ethanol-free. On day 16 the rats received 25 mg of thiopental per kilogram (intravenously). One minute after the injection, the ethanol-treated rats showed lower blood levels of thiopental and higher liver levels of the drug than control rats given sucrose in place of ethanol. Samples of blood drawn 5 and 10 min after injection showed no significant difference in thiopental levels between the ethanol and control groups. The ethanol-treated group slept for a significantly shorter period of time. It is concluded that chronic ethanol consumption for 14 days decreases the pharmacological effects of thiopental and alters its initial distribution in the body.     

Validation of a mathematical model of the bovine estrous cycle for cows with different estrous cycle characteristics

A recently developed mechanistic mathematical model of the bovine estrous cycle was parameterized to fit empirical data sets collected during one estrous cycle of 31 individual cows, with the main objective to further validate the model. The a priori criteria for validation were (1) the resulting model can simulate the measured data correctly (i.e. goodness of fit), and (2) this is achieved without needing extreme, probably non-physiological parameter values. We used a least squares optimization procedure to identify parameter configurations for the mathematical model to fit the empirical in vivo measurements of follicle and corpus luteum sizes, and the plasma concentrations of progesterone, estradiol, FSH and LH for each cow. The model was capable of accommodating normal variation in estrous cycle characteristics of individual cows. With the parameter sets estimated for the individual cows, the model behavior changed for 21 cows, with improved fit of the simulated output curves for 18 of these 21 cows. Moreover, the number of follicular waves was predicted correctly for 18 of the 25 two-wave and three-wave cows, without extreme parameter value changes. Estimation of specific parameters confirmed results of previous model simulations indicating that parameters involved in luteolytic signaling are very important for regulation of general estrous cycle characteristics, and are likely responsible for differences in estrous cycle characteristics between cows.     

Intramaze cue utilization in the water maze: effects of sex and estrous cycle in rats

Rats can use a wide spectrum of intra- and extramaze information while navigating through the environment. The current study examined the relative contribution of an intramaze cue with regard to its proximity to the goal. Three experiments were conducted and the impact of intramaze cue removal or rotation on water maze search was examined. In males, the effect of the intramaze cue declined monotonically in relation to the proximity of the cue to the goal. A more complex relationship between cue location and utilization was found in estrous and proestrus females. Estrous females showed a strong effect of the cue only when it was near the goal, ignoring it when it was situated further away. Conversely proestrus females were affected by the cue under all conditions. It is concluded that previous reports of behavioral differences may stem from the fact that proestrus females are affected by and attend to a wider range of stimuli, while estrous females are more affected by salient stimuli.     

The influence of steroids on vascular tension of isolated superficial veins of the nose and face during the estrous cycle of gilts

The arrangement of the superficial facial veins enables blood flow from the nasal cavity into the peripheral circulation by two pathways: through the frontal vein into the cavernous sinus and through the facial vein into the external jugular vein. The current study was designed to determine whether estradiol and progesterone affect the vascular tone of the superficial veins of the nose and face in cycling gilts (Sus scrofa f. domestica) and to analyze the immunolocalization of progesterone receptors and estradiol receptors in these veins. The influence of hormones on vascular tension differed depending on the type of vessel and the phase of the estrous cycle. Estradiol decreased vascular tension in the nasal vein during the follicular phase (P < 0.05) and increased tension in the frontal vein during the luteal phase (P < 0.05). Progesterone increased the vascular tension of the frontal vein (P < 0.05) and decreased the tension of the other veins (P < 0.05) in both phases of the cycle. Expression of estradiol receptor β but not of progesterone receptor was observed in the superficial veins of the nose and face. In conclusion, the effect of ovarian steroid hormones on the vascular tension of the superficial veins of the nose and face in female pigs as well as the reactivity of these veins to steroid boar pheromones can affect the blood supply from the nasal cavity to the venous cavernous sinus. We propose that the ovarian steroid hormones that modulate the vascular tension of the nasal and facial veins may also influence the action of boar pheromones absorbed into the nasal mucosa in gilts and may reach the brain via local destination transfer.     

The influence of the estrous cycle on the volume density and appearance of collagen containing vacuoles in fibroblasts of the rat uterus

The influence of the estrous cycle on the number of intracellular collagen-containing vacuoles (CCVs) has been studied in the uterus of the virgin Wistar rat. CCVs seem to be involved in two processes. Translucent CCVs dark CCVs and dark residual bodies appear to be involved in collagen uptake and degradation, whilst the so-called filamentous bodies (FBs), which are large structures filled with amorphous filaments may be concerned with collagen synthesis. The volume density of these FBs is influenced by the estrous cycle and peak values are accompanied by the highest values of extracellular collagen.     

The estrous cycle in the dog: a review

Clinical, morphologic and hormonal changes throughout the estrous cycle in the dog are discussed in relation to the well established stages in this species — proestrus, estrus, metestrus and anestrus. Although most efforts in the past have been devoted to the period of reproduction, events throughout the remaining months of the cycle are presented to characterize the dog as a monocyclic animal in contrast to polycyclic species.     

The behaviour of rats selected for their voluntary ethanol consumption

New strains of rats, preferent (HAP) and non-preferent (NAP) for ethanol were selectively outbred from a Wistar stock. The strains have now been raised to the F13 generation. The F9/10 animals, selected for this behavioural investigation, exhibited a significant phenotypic drinking behaviour and/or ethanol consumption. During a free choice between tap water and 10% ethanol solution (v/v), the mean daily alcohol intake for male and female HAP rats was 8.42 +/- 0.69 g/kg/24 h (n = 20 o) and 11.50 +/- 0.42 g/kg/24 h (n = 20 o), for male and female NAP rats 0.74 +/- 0.09 g/kg/24 h (n = 20 o) and 1.76 +/- 0.20 g/kg/24 h (n = 20 o), respectively. The NAP rats exhibited a strong aversion to the 10% ethanol solution when it was the only source fluid. In the open-field test (OFT), as compared to the NAP rats, male individuals of the HAP strain showed a lower motility in the first minute, in penetration into the inner squares, showed a longer latency to start exploration (latency to leave the center), exhibited larger rearing and grooming activity and shorter latencies to start these activities. The defecation rate was smaller and latency to defecation prolonged. Female HAP rats showed higher activity scores in penetration of outer and inner squares and a shorter latency to start exploration. They also had higher rearing but smaller grooming activity. The females exhibited identical defecation but different urination behaviour in comparison to the males. The time-to-emerge latencies of HAP rats were longer than in NAP individuals.     

Effect of season on estrous cycle of Yankasa sheep

An investigation was conducted to establish the effects of harmattan and hot-dry season on estrous cycle length, onset, and duration of estrus in Yankasa sheep indigenous to the Nigerian guinea savanna zone. Mean cycle lengths were 16.8 +/- 0.58 and 16.4 +/- 0.53 days during harmattan and hot-dry seasons, respectively; short cycles, 5-13 days, and long cycles, 21 to 30 days, were observed during both seasons. During the harmattan season, 57.1% of estrus began at night while 70% started at night during the hot-dry season. The duration of normal estrus observed during the harmattan, 33.6 +/- 5.87h, significantly decreased (P0.05) during the hot-dry season (24.0 +/- 5.45h). It is suggested that twice daily observation at 12-hour intervals will suffice to detect estrus in this breed of sheep.     

The estrous cycle of captive woodchucks (Marmota monax)

Changes in vaginal cytology were assessed and correlated with temporal changes in circulating concentrations of progesterone (P) and estradiol-17 beta (E2) during the breeding season (February to March) in a seasonally breeding rodent, the woodchuck (Marmota monax). Ten individually caged adult females, maintained under laboratory conditions for 3-11 mo, were studied. Vaginal smears were taken each morning for 2 consecutive months beginning 1 February 1990. Seven of 10 females exhibited readily identifiable estrus, characterized by a clear predominance (83%) of cornified cells. The earliest estrous smear was recorded on 3 February and the latest on 12 March. These animals were monoestrous and remained in a prolonged estrous period during their brief breeding season. The average duration of estrus was 18.1 +/- 2.1 days, ranging from 12-27 days. Levels of P and E2 were determined in serum samples taken before, during, and after estrus from 7 females who exhibited estrus. No changes in the circulating levels of P were apparent during the estrous cycle. However, there was a consistent pattern of estradiol secretion characterized by elevated levels of E2 before and during estrus, followed by a significant (p less than 0.05) decline in E2 levels one week after the end of estrus. Elevated levels of E2 preceded and coincided with maximal degree of vaginal cornification. Thus, the termination, but not the onset, of estrus in woodchucks reflected closely the temporal pattern of changes in serum E2 levels during the breeding season.     

The influence of age and sex on phagocyte chemiluminescence

The process of ageing is associated with increased susceptibility to infection. Phagocytes form the primary defence mechanism against infecting microorganisms, but the influence of ageing on phagocyte function remains controversial. In this study we have applied a microtitre plate phagocyte chemiluminescence (CL) assay suitable for clinical use to compare phagocyte oxidative metabolism in younger healthy subjects (age 20–60 years) and healthy older (60–70 years) subjects. Polymorphonuclear leukocytes (PMNL) and monocytes were stimulated using phorbol myristate acetate (PMA), serum opsonized zymosan (SOZ), and non-opsonized zymosan (ZYM) in the presence of both lucigenin and luminol. Monocytes showed a higher luminolenhanced CL response to PMA in males compared with females in the younger age group. No PMNL differences were observed between the sexes. Although no difference were found in relation to age when cells were stimulated with PMA and SOZ, significantly lower background (unstimulated) CL was obtained from PMNL with luminol. PMNL luminol-enhanced CL responses were also lower in response to ZYM. The findings suggest a reduced response of PMNL from older subjects to minimal stimulation. This could be related to abnormalities in the triggering of the respiratory burst or myeloperoxidase release due to ageing. The influence of age and sex should be taken into account in clinical studies of phagocyte CL.