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Sex differences in the inhibitory effects of the NMDA antagonist, MK-801, on morphine and stress-induced analgesia.

We examined the effects of intraperitoneal administrations of the noncompetitive NMDA receptor antagonist, (+) MK-801, its inactive enantiomer, (-) MK-801, and the prototypic opiate antagonist, naloxone, on restraint- and morphine-induced analgesia in male and female deer mice, Peromyscus maniculatus. Both restraint (30 min) and morphine (1.0 mg/kg) induced significant analgesic responses with male mice displaying significantly greater levels of opioid-induced analgesia than female animals. These analgesic responses were completely blocked by, naloxone (1.0 mg/kg), significantly reduced by (+) MK-801 (0.25 mg/kg) and unaffected by (-) MK-801 (0.25 mg/kg) pretreatments. There were significant male-female differences in the inhibitory effects of (+) MK-801; the higher levels of morphine- and restraint-induced analgesia of the males were completely blocked, while the lower level analgesic responses of the females were significantly reduced, but not blocked, by (+) MK-801. These observations provide further evidence that NMDA receptors are involved in the mediation of endogenous and exogenous opioid analgesia and show that there are significant male-female differences in the inhibitory effects of (+) MK-801 on opioid-mediated analgesia.

Analgesia↗

Borrelia burgdorferi infection in dairy cows, rodents, and birds from four Wisconsin dairy farms.

A combination of culture and subsequent spirochete identification with the polymerase chain reaction technique was used to identify cows, rodents, and birds infected with Borrelia burgdorferi. Animals were trapped on four Wisconsin dairy farms during the summer of 1990. Farms 1 and 2 were located in counties nonendemic for Lyme disease and Farms 3 and 4 were located in counties endemic for Lyme disease. The results of the rodent and bird samples were as follows given as the number yielding organisms number tested: Farm 1, 1/17 Mus musculus and 2/52 Peromyscus domesticus; Farm 2, 4/49 M. musculus, 1/2 P. maniculatus, 1/1 P. leucopus, and 1/35 P. domesticus; Farm 3, 0/27 M. musculus, 0/5 P. leucopus, 0/12 P. maniculatus and, 3/58 P. domesticus; and Farm 4, 1/24 M. musculus, 2/19 P. leucopus, 1/12 Microtus pennsylvanicus, and 0/17 P. domesticus. One P. leucopus and one M. musculus from Farm 2 were pregnant and fetal tissues from both were positive. Cow blood sample results were as follows: Farm 1, 7/47 in July, and 2/45 in August; Farm 2, 0/28 in August and 0/23 in October; Farm 3, 0/13 in July and 1/18 in August 29; and Farm 4, 3/45 in August. Ticks were found on rodents on Farm 4 and on one bird on Farm 3. Spirochetemic cows, rodents, and birds were found in non-Lyme endemic counties suggesting that alternate modes of transmission other than by ticks may be important. Transplacental transmission was shown in M. musculus and P. leucopus.

Animals↗

Organophosphorus insecticide induced decrease in plasma luteinizing hormone concentration in white-footed mice.

Oral intubation of 50 and 100 mg/kg acephate inhibited brain acetylcholinesterase (AChE) activity by 45% and 56%, and reduced basal luteinizing hormone (LH) concentration by 29% and 25% after 4 h in white-footed mice (Peromyscus leucopus noveboracensis). Dietary exposure to 25, 100, and 400 ppm acephate for 5 days substantially inhibited brain AChE activity, but did not affect plasma LH concentration. These preliminary findings suggest that acute exposure to organophosphorus insecticides may affect LH secretion and possibly reproductive function.

Acetylcholinesterase↗

Analysis of supercoiled circular plasmids in infectious and non-infectious Borrelia burgdorferi.

Linear plasmids are widely distributed in isolates of Borrelia burgdorferi, but the prevalence of supercoiled circular (SC) plasmids has not been clearly established. Enriching for SC plasmids on ethidium bromide density-gradients revealed that a low passage of strain Sh-2-82 of B. burgdorferi has at least six SC plasmids (8.4, 8.8, 20, 26, 29 and 51 kb). In addition, several of the SC plasmids were observed by electron microscopy to form concatenated structures. Because of the high incidence of coupled SC plasmids and the effect of such structures on plasmid mobility, we suggest that they could be mistaken for a single DNA species having a high molecular weight when total DNA from B. burgdorferi is examined by agarose-gel electrophoresis. Of the six SC plasmids in strain Sh-2-82, four could still be detected after two years of continuous in vitro passaging in BSK II medium. The two SC plasmids lost after a maximum of 20 passages, pBBC1 (8.4 kb) and pBBC2 (8.8 kb), shared a high degree of DNA sequence similarity, suggesting that their apparent instability may be a unique feature of these closely related plasmids. Two higher passaged variants of strain Sh-2-82, P20 and P202, were shown by hybridization to lack pBBC1 and pBBC2 sequences and were unable to infect the white-footed mouse, Peromyscus leucopus. However, six of 14 unrelated isolates that infected this rodent and Syrian hamsters also lacked pBBC1 and pBBC2 sequences. None of five unrelated but highly passaged non-infectious isolates carried either pBBC1 or pBBC2 sequences. These data indicate that pBBC1 and pBBC2 do not encode constitutively expressed proteins required for infectivity in our experimental system. Nevertheless, eight of the 13 infectious strains examined did carry pBBC1 and/or pBBC2, indicating that these two closely related plasmids can be detected in a wide range of unrelated isolates of B. burgdorferi.

Animals↗

Age-dependent characterization of pendrin gene expression in various tissues of deer mice.

Pendrin is a membrane transport protein which functions as the transporter of chloride, bicarbonate, formate, and iodide. In this study, we characterized pendrin gene expression in various tissues of deer mice (Peromyscus maniculatus), a sentinel wildlife species. Deer mice were euthanized at post-natal day (PND) 21 (day of weaning) and PND 45 (24 days post-weaning) for tissue collection. A deer mouse-specific partial pendrin cDNA sequence was generated, from which Taqman-specific probe and primers were designed for quantification of mRNA equivalents of pendrin gene expression using real-time polymerase chain reaction (PCR). The expression profile was standardized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Results indicate that the pendrin gene was expressed at different levels in the different tissues of developing deer mice relative to GAPDH expression. Expression in the tissues was determined to be age-dependent. Pendrin gene was highly expressed in the kidney, lungs and reproductive tissues. PND 21 expression in the kidney and testes was significantly lower than PND 45. This study represents the first identification of differential expression of pendrin gene in various deer mouse tissues.

Aging↗

Reduced free-radical production and extreme longevity in the little brown bat (Myotis lucifugus) versus two non-flying mammals.

The extended longevity of bats, despite their high metabolic rate, may provide insight to patterns and mechanisms of aging. Here I test predictions of the free radical or oxidative stress theory of aging as an explanation for differences in lifespan between the little brown bat, Myotis lucifugus (maximum lifespan potential MLSP=34 years), the short-tailed shrew, Blarina brevicauda (MLSP=2 years), and the white-footed mouse, Peromyscus leucopus (MLSP=8 years) by comparing whole-organism oxygen consumption, hydrogen peroxide production, and superoxide dismutase activity in heart, kidney, and brain tissue. Mitochondria from M. lucifugus produced half to one-third the amount of hydrogen peroxide per unit of oxygen consumed compared to mitochondria from B. brevicauda and P. leucopus, respectively. Superoxide dismutase (SOD) activity did not differ among the three species. These results are similar to those found for birds, which like bats have high metabolic rates and extended longevities, and provide support for the free radical theory of aging as an at least partial explanation for the extreme longevity of bats.

Animals↗

c-fos Changes following an aggressive encounter in female California mice: a synthesis of behavior, hormone changes and neural activity.

Although there has been growing interest in the neuroanatomical and physiological mechanisms underlying aggressive behavior, little work has focused on possible mechanisms controlling natural plasticity in aggression. In the current study, we used naturally occurring changes in aggression level displayed by female Peromyscus californicus across the estrous cycle and parallel changes in c-fos expression to examine possible brain regions involved in mediating this plasticity. We found that c-fos expression was increased in females exposed to a conspecific female intruder compared with control females in numerous brain regions thought to be involved in the control of aggression. More importantly, we found that c-fos increased in the bed nucleus of the stria terminalis (BNST) and ventral lateral septum (LSv) only in the more aggressive, diestrous females, and not in the less aggressive, proestrous and estrous females. Conversely, c-fos increased in the medial amygdala (MeA) across all stages of estrus compared with controls, suggesting the MeA is not involved in mediating changes in individual levels of aggression. Moreover, we found correlations between several measures of aggression and c-fos expression in the BNST and LSv but not the MeA, again suggesting a role in mediating aggression plasticity for the former two but not the latter brain region. We further hypothesize that the BNST and the LSv may be involved more generally in mediating natural changes in aggression, such as increases often observed after individuals win aggressive interactions against conspecifics.

Aggression↗

Opposing hormonal mechanisms of aggression revealed through short-lived testosterone manipulations and multiple winning experiences.

Territorial aggression is influenced by many social and environmental factors. Since aggression is a costly behavior, individuals should account for multiple factors such as population density or reproductive status before engaging in aggression. Previous work has shown that male California mice (Peromyscus californicus) respond to winning aggressive encounters by initiating aggression more quickly in future encounters, and we investigated the physiological basis for this effect. We found that injections that produced a transient increase in testosterone (T) following an aggressive encounter caused males to behave more aggressively in an encounter the following day. Experience alone was not enough to change aggression, as males treated with saline injections showed no change in aggression. The effect of T injections on aggression was androgen-based, as the inhibition of aromatase did not block the T injections from increasing aggression. Aromatase inhibition did, however, increase aggression in the initial aggression tests (before application of T or saline injections), and aromatase activity in the bed nucleus of the stria terminalis (BNST) was negatively correlated with aggression. A previous study suggested that aromatase activity in the BNST decreases after males become fathers. Thus, distinct neuroendocrine mechanisms allow male California mice to adjust aggressive behavior in response to changes in social and reproductive status.

Aggression↗

Winning fights elevates testosterone levels in California mice and enhances future ability to win fights.

The 'winner effect' has been studied in a variety of species, but only rarely in mammals. We compared effects of winning three, two, one, or zero resident-intruder encounters on the likelihood of winning a subsequent aggressive encounter in the California mouse (Peromyscus californicus). During the training phase, we ensured that resident males won all encounters by staging contests with mildly sedated, smaller intruders. During the test phase, the resident male encountered an unfamiliar, more evenly matched intruder that had experience winning an encounter and was larger than the resident. Testosterone (T) plasma levels significantly increased after the final test when they had experienced two prior winning encounters, and the probability of winning a future encounter increased significantly after three prior wins independent of intrinsic fighting ability. We hypothesize a 'winner-challenge' effect in which increased T levels serve to reinforce the winner effect in male California mice.

Aggression↗

Paternal behavior influences development of aggression and vasopressin expression in male California mouse offspring.

Parental care has been demonstrated to have important effects on offspring behavioral development. California mice (Peromyscus californicus) are biparental, and correlational evidence suggests that pup retrieving by fathers has important effects on the development of aggressive behavior and extra-hypothalamic vasopressin systems. We tested whether retrievals affected these systems by manipulating paternal retrieval behavior between day 15 and 21 postpartum. Licking and grooming behavior affect behavioral development in rats, so we also experimentally reduced huddling and grooming behavior by castrating a subset of fathers. Experimentally increasing the frequency of paternal pup retrieving behavior decreased attack latency in resident-intruder in both male and female adult offspring, whereas experimental reduction of huddling and grooming had no effect. In a separate group of male offspring, we examined vasopressin immunoreactivity (AVP-ir) in two regions of the posterior bed nucleus of the stria terminalis (BNST): the dorsal fiber tracts (dBNST) and the ventral cell body-containing region (vBNST). Experimentally increasing retrievals led to an apparent shift in AVP-ir distribution. Specifically, offspring from the high retrieval group had more AVP-ir than offspring from the sham retrieval group in the dBNST, whereas the opposite was observed in the vBNST. Experimental reduction of paternal grooming was associated with increased AVP-ir in the paraventricular nucleus and also increased corticosterone and progesterone, similar to observed effects of maternal grooming on HPA function. This study provides further evidence that paternal behavior influences the development of aggression and associated neural substrates.

Aggression↗

Aggressive behaviour of female prairie deer mice in laboratory populations.

Prairie deer mice (Peromyscus maniculatus bairdii), living in asymptotic laboratory populations established two years earlier, were observed for agonistic responses to conspecific intruders. In the first experiment, intruders of six age-sex classes were placed into 10 of the populations for 10 min. The sex of the intruder did not influence the behaviour of the residents, but juveniles elicited more regression than did adults. A second experiment revealed that female residents were responsible for almost all of the attacks upon juveniles. Experiment 3, in which the responses of pairs of deer mice to juvenile intruders were recorded, demonstrated that the aggressiveness of a female was enhanced by the presence of a male. In the final experiment, females were observed to be highly aggressive during the first few days after giving birth. The aggressive behaviour of the female deer mouse may have greater significance for population dynamics than that of the male.

Age Factors↗

Water-deprived white-footed mice express c-fos on a day/night cycle graded according to the duration of deprivation.

Mammals respond to electrolyte and water imbalance by a variety of neural and endocrine mechanisms that regulate water and salt intake and loss. We used the expression of c-fos and Fos-related antigens to indicate neuronal activation in hypothalamic neurons of members of an outbred laboratory population of white-footed mice (Peromyscus leucopus) deprived of water for biologically reasonable periods of time (6-18 h). We examined Fos-like immunoreactivity (Fos-LIR) in the supraoptic nucleus (SON) and paraventricular nucleus (PVN). During the dark period, when these animals are normally active, 6 h of water deprivation produced near-maximal increases in the number of cells positive for Fos-LIR in the SON and PVN. In contrast, during the light period, when these mice are normally inactive and do not have access to water, 6 h of water deprivation only slightly affected Fos-LIR. During the day, it required as much as 12 h of water deprivation to produce increases in Fos-LIR cells approaching those achieved at night. Plasma osmolarity was directly related to the number of Fos-LIR cells. In addition, mice lost weight more rapidly at night than during the day when water-deprived, and also recovered that lost weight more rapidly when access to water was returned. Our results show (1) that biologically reasonable levels of water restriction (and resulting changes in blood osmolarity) induce changes in Fos-LIR in this wild mouse species, and (2) that these mice have a daily cycle of sensitivity to water deprivation that is demonstrated by both behavioral, psychological and immunohistological assessment of reactions to water deprivation.

Analysis of Variance↗

Experimental evidence of host specificity of Bartonella infection in rodents.

A large number of Bartonella species and genetic variants were compared for their ability to cause bacteremia in different rodent species: the cotton rat (Sigmodon hispidus), white-footed mouse (Peromyscus leucopus), BALB/c mouse and Wistar rat. Experimental data supported field observations that host specificity can occur among certain Bartonella species and rodent species. Bacteremia could only be readily produced in cotton rats or white-footed mice if the strains used for inoculation were originally obtained from the same species or from a phylogenetically close species. A few Bartonella colonies could be observed in the blood of some BALB/c mice by 7 days after inoculation, but no evidence of the persistence of the infection was found. Host specificity suggests the possibility of a long co-speciation of Bartonella species with their rodent hosts. Host-parasite relationships measured by the duration and level of bacteremia and the minimal infectious dose may serve as additional criteria for classification of Bartonella isolates obtained from natural environments.

Animals↗

The prevalence and significance of Borrelia burgdorferi in the urine of feral reservoir hosts.

Live Borrelia burgdorferi were isolated from the blood and/or urine of white-footed mice (Peromyscus leucopus) collected on Shelter Island, New York, in 1984 and 1985. Prevalence of spirochetes in urine was consistently higher than in blood or both fluids simultaneously. Spirochetes remained viable for 18-24 hours in urine and were maintained in culture for one week. Mice removed from the field were spirocheturic for at least 13 months. One spirocheturic mouse developed spirochetemia one month after field removal indicating the pathogen can return to the peripheral circulation. Twenty-one kidneys from 22 mice had spirochetes in the interstitial areas and bridging the tubules. A positive correlation between Babesia microti infection and spirocheturia was seen. Although the mechanism of entry into the urine is unknown, B. microti infection may increase glomerular permeability. Babesia induced hematuria may provide possible nutrients to maintain spirochetes. Urine may provide a method for contact non-tick transmission of B. burgdorferi in natural rodent populations particularly during periods of nesting and/or breeding.

Animals↗

Comparison of white-footed mice and rice rats as biomonitors of polychlorinated biphenyl and metal contamination.

A study was conducted to assess differences in contaminant assimilation among co-occurring white-footed mice (Peromyscus leucopus) and rice rats (Oryomys palustris) captured at a contaminated site. Rodents were collected from five areas at the Paducah Gaseous Diffusion Plant (PGDP), a uranium enrichment facility. Relatively few white-footed mice (8.7%) had quantifiable concentrations of PCBs compared to 42% of rice rats (chi2 = 6.49, d.f. = 1, P < 0.025), and seven of the 11 rice rats (64%) over 50 g body mass had quantifiable concentrations of PCBs in their livers. White-footed mice had higher mean concentrations of barium (P < 0.0001), chromium (P = 0.0010), copper (P = 0.0011), lead (P = 0.0335), and aluminum (P = 0.0006) than rice rats at all five sampling areas. Species-specific differences in accumulation of PCBs and metals were observed and attributed to differences in habitat use and foraging strategies.

Animals↗

Entrainment impaired, masking spared: an apparent genetic abnormality that prevents circadian rhythm entrainment to 24-h lighting cycles in California mice.

Lighting cycles can influence the expression of daily activity rhythms in two ways: by entraining the circadian pacemaker that normally drives this rhythm, and by directly affecting the expression of activity itself, thereby 'masking' the influence of the pacemaker. We describe a California mouse (Peromyscus californicus) in which these processes are dissociated. Circadian rhythms of wheel-running activity were recorded continuously while the animal was housed in a standard light/dark cycle and in constant darkness. This animal expressed a normal circadian rhythm that failed to entrain to the light/dark cycle, but was completely masked during the light phase. This animal's phenotype appears to have a genetic basis, since the progeny of selective crosses of his descendants showed similar abnormalities. These mice are the first example of animals expressing apparently normal circadian rhythms that are not entrained by light, but that still show potent masking responses to light exposure.

Animals↗

Sex differences in opioid and N-methyl-D-aspartate mediated non-opioid biting fly exposure induced analgesia in deer mice.

There is evidence for sex differences in responses to noxious stimuli and in the expression and mediation of analgesia. In particular, results of investigations with swim stress and the more ethologically appropriate stress of predator odor exposure have suggested sex differences in N-methyl-D-aspartate (NMDA) receptor system involvement in the mediation of analgesia. Whether or not this sex difference generalizes to other environmental stressors is, however, not clear. Biting flies are a natural aversive stimuli commonly encountered by wild and domestic animals and humans. The present study examined the opioid and non-opioid mediated nociceptive (50 degrees C hot plate) responses of reproductive male and female deer mice, Peromyscus maniculatus, exposed to biting fly attack. A 30 min exposure to biting flies (stable flies, Stomoxys calcitrans (L.)) elicited a naloxone sensitive, opioid-mediated analgesia that was of a greater magnitude in males than in female deer mice. In contrast, a 5 min exposure to biting flies elicited a 'on-opioid' analgesia that was of similar magnitude in both sexes and insensitive to both naloxone and the specific kappa opiate antagonist, nor-binaltorphimine. In male mice this non-opioid analgesia was antagonised by the competitive NMDA antagonist, NPC 1262, while in reproductive females the biting fly-induced analgesia was insensitive to NPC 12626. These results show that there are sex differences in NMDA involvement in the mediation of the non-opioid analgesia arising from brief exposure to the stress of biting fly attack. These data from a common, natural environmental challenge support the presence of basic sex difference in NMDA involvement in the mediation of stress-induced analgesia.

Amino Acids↗

Spatial learning and hippocampal volume in male deer mice: relations to age, testosterone and adrenal gland weight.

Spatial learning and various physiological parameters were examined in old (57 month), middle aged (38 month), adult (18 month) and young (3-3.5 month) male deer mice (Peromyscus maniculatus). Performance during acquisition of a water maze task was not significantly reduced for middle aged and adult mice relative to young reproductively active (breeding) mice. Performance was deteriorated in old mice relative to young breeding mice on block 4 of training. Retention of this spatial task, however, was reduced in all three older groups relative to young breeding mice. Corrected hippocampal volume (corrected for brain weight) was reduced only in old mice relative to young breeding mice although absolute volumes of hippocampus were lower in all groups relative to young breeding mice. Old mice also were shown to have lower levels of plasma testosterone and lighter brains relative to young breeding mice. Spatial retention was not deficient in old, middle aged and adult mice relative to a group of young reproductively quiescent male (non-breeding) mice. Young breeding mice displayed better spatial performance and had significantly higher plasma testosterone levels, corrected hippocampal volume and brain weight relative to young non-breeding mice. These results indicate that retention of a spatial task is more sensitive to the age of male deer mice than acquisition of the task. Hippocampal volume, although a gross morphological feature, appears to be sensitive to the effects of ageing in male deer mice. Plasma testosterone levels do not appear to be a crucial factor underlying age-related deficits in retention of a spatial task.

Adrenal Glands↗