Biomedical subjects

M Kavaliers

Publications and source records attributed to M Kavaliers.

At least 19 recordsLinked to original sources

PubMed1999

Brief predator odour exposure activates the HPA axis independent of locomotor changes.

Although predator exposure has been proposed to elicit both behavioural responses and neuroendocrine effects in rodents, results of an increasing number studies have failed to consistently detect both of these alterations. We provide a detailed multivariate quantitative assessment of locomotor activity levels and plasma levels of adrenocorticotrophic hormone (ACTH) and corticosterone of male and female laboratory rats following brief (5 min) exposure to a predator odour, (2-propylthietane, the main constituent of weasel anal gland secretion). We show that there is a clear distinction between the behavioural and neuroendocrine responses, with predator odour inducing significant increases in corticosterone and ACTH levels without any significant accompanying changes in various locomotor activity measures.

Adrenocorticotropic Hormone↗

PubMed1999

Relations of hippocampal volume and dentate gyrus width to gonadal hormone levels in male and female meadow voles.

The present study examined hippocampal volume and dentate gyrus width and their relations to gonadal hormone levels in adult male and female meadow voles, Microtus pennsylvanicus. Females were split into High and Low Estradiol groups based on the median estradiol level. Males were similarly split into High and Low Testosterone groups. Contrary to previous reports in wild meadow voles, there was no evidence of an overall sex difference in hippocampal volume. However, when male-female comparisons were limited to High Testosterone males and Low Estradiol females a significant sex difference in hippocampal volume favouring males did emerge. Hippocampal volume in males was related to testosterone level, with High Testosterone males having significantly larger hippocampi than Low Testosterone males. Similarly, there was a significant influence of plasma estradiol level on hippocampal volume and left dentate gyrus width, with High Estradiol females having larger hippocampi and dentate gyrus width than Low Estradiol females. In addition, consistent with previous findings in the laboratory rat, there were sex differences favouring males in right dentate gyrus width. These findings show that there is a complex relationship between hippocampal volume, dentate gyrus width and gonadal hormone levels in male and female meadow voles.

Animals↗

PubMed1999

Learning to cope with biting flies: rapid NMDA-mediated acquisition of conditioned analgesia.

A 30-min exposure to intact biting flies (stable flies) induced an opioid-mediated analgesia in fly-naive male deer mice, whereas exposure to either altered biting flies whose biting mouthparts were removed or nonbiting house flies had no significant effects. However, mice that were previously exposed to intact stable flies for 30 min exhibited significant analgesia when exposed 24-168 hr later to stable flies whose biting parts were removed, but not to nonbiting house flies. Administration of the specific N-methyl-D-aspartate (NMDA) antagonist NPC 12626 to fly-naive mice before exposure to intact flies, although not significantly reducing the analgesic response, blocked the subsequent conditioned analgesia. Naloxone, which blocked the intact biting fly-induced analgesia, did not alter the acquisition of the conditioned analgesic response to the altered stable flies. This demonstrates an NMDA-mediated acquisition of conditioned analgesia to a natural aversive stimulus.

Adaptation, Physiological↗

PubMed1998

Brief exposure of mice to 60 Hz magnetic fields reduces the analgesic effects of the neuroactive steroid, 3alpha-hydroxy-4-pregnen-20-one.

Relatively weak, extremely low frequency (ELF), magnetic fields have been shown to exert a variety of biological effects, although the modes of action remain to be established. Neuroactive steroids and neurosteroids have been shown to produce a diverse range of rapid centrally mediated behavioral and physiological effects that are reported to be sensitive to magnetic fields. Here we show that brief exposure of male mice to an ELF magnetic field (30 min, 60 Hz, 141 microT peak) significantly reduces the analgesic effects arising from intracerebroventricular (i.c.v.) administration of the centrally produced allylic neuroactive steroid, 3alpha-hydroxy-4-pregnen-20-one (3alphaHP) and that the dihydropyridine (DHP) calcium channel antagonists, diltiazem and nifedipine, block the inhibitory effects of the 60 Hz ELF on 3alphaHP-induced analgesia. These results indicate that exposure to 60 Hz ELF affects the analgesic effects of neuroactive steroids such as 3alphaHP through alterations in calcium channel function. These findings raise the possibility that ELF magnetic fields may, in part, exert their actions through effects on diverse neuroactive steroid modulated processes.

20-alpha-Dihydroprogesterone↗

PubMed1998

Individual differences in radial maze performance and locomotor activity in the meadow vole, Microtus pennsylvanicus.

Individual differences in the radial maze performance and locomotor activity of wild-caught and first-generation laboratory-born meadow voles are described. Based on their patterns of response in an eight-arm radial maze the essentially wild voles fell into three behavioral categories: 1) strict algorithmic (i.e., they systematically chose the next adjacent arm to their previous choice); 2) nonalgorithmic (i.e., they ran the maze without any consistent or definable pattern); and 3) nonrunners (i.e., nonperformers of the task who remained relatively immobile in the arms of the maze). The algorithmic and nonalgorithmic voles further differed in their responses to an interference manipulation of the radial maze task. Algorithmic individuals displayed a marked performance deficit, while the nonalgorithmic individuals showed minimal disruption to a 1-min delay interruption of the maze task. Measurements of several aspects of locomotor activity using the automated Digiscan activity monitoring system revealed that the algorithmic individuals also displayed significantly greater levels of activity than the nonalgorithmic or nonrunners, with no significant difference in activity between the latter two groups. These findings suggest that the algorithmic voles were relatively inflexible in their behavior, while the nonalgorithmic individuals were more flexible in their maze performance and likely in their use of spatial and nonspatial information. These individual differences in laboratory measures of learning behavior and locomotor activity in meadow voles are consistent with the polymorphism that is proposed to occur in the wild.

Animals↗

PubMed1998

Sex differences in spontaneous locomotor activity and rotational behavior in meadow voles.

Sex differences in rotational behavior have been most clearly established in laboratory rats with females exhibiting a turning bias. Here, using an automated open-field apparatus, locomotor activity and spontaneous rotational behavior were examined in diurnally crepuscularly active reproductive male and female meadow voles (Microtus pennsylvanicus). Meadow voles, being induced ovulators, permitted analysis of females in constant behavioral estrous. Males displayed significantly greater levels of activity and also significantly greater levels of clockwise but not counterclockwise rotational behavior relative to the females. Rotational behavior was less strongly related to activity levels in female as compared to male voles. In addition, females displayed an overall turning bias. These results contrast with findings from laboratory rats in which females are reported to display greater levels of both locomotor activity and rotational behavior. They are, however, consistent with the rotational bias evident in female rats. The present findings confirm the presence of sex differences in rotational behavior and indicate that factors other than activity levels are involved in the generation and/or expression of these sex differences. Sex differences in anxiety and routine-like behavior (i.e., asymmetry in movement) are discussed as possible factors contributing to these male-female differences in rotational behavior.

Animals↗

PubMed1998

Sex differences in spatial learning and prefrontal and parietal cortical dendritic morphology in the meadow vole, Microtus pennsylvanicus.

The prefrontal and parietal cortex has been implicated in the mediation of spatially related behaviors in male and female laboratory rats. Meadow voles, Microtus pennsylvanicus, are diurnally-crepuscularly active microtine rodents that exhibit a variety of sexually dimorphic spatially associated behaviors in both the laboratory and wild. In the present study we examined both the spatial Morris water maze performance and dendritic architecture and branching of neuronal cells in the prefrontal and parietal cortex of reproductive male and female meadow voles. Males learned the location of the hidden platform in the water task faster than estrous females and on probe trials they spent more time in the previously correct quadrant than females. Dendritic analysis with Golgi-Cox stained sections showed that male voles had significantly more dendritic arborization in the medial prefrontal and parietal cortex than females. These sex differences in both spatial navigation ability and in neural structures related to spatial navigation in meadow voles suggest that the size of neural areas might be shaped by ecological pressures associated with sexually dimorphic spatial behaviors.

Animals↗

PubMed1998

Evidence for the involvement of nitric oxide and nitric oxide synthase in the modulation of opioid-induced antinociception and the inhibitory effects of exposure to 60-Hz magnetic fields in the land snail.

The attenuation of opioid peptide-mediated antinociception is a well-established effect of extremely low frequency (ELF) electromagnetic fields with alterations in calcium channel function and/or calcium ion flux and protein kinase C activity being implicated in the mediation of these effects. The present study was designed to examine the effects of nitric oxide (NO) and calcium ion/calmodulin-dependent nitric oxide synthase (NOS) on opioid-induced antinociception and their involvement in mediating the inhibitory effects of exposure to ELF magnetic fields. We observed that enkephalinase (SCH 34826)-induced, and likely enkephalin-mediated, antinociception in the land snail, Cepaea nemoralis, as measured by the enhanced latency of a foot withdrawal response to a thermal (40 degreesC) stimulus, was reduced by the NO releasing agent, S-nitro-N-acetylpenicillamide (SNP), and enhanced by the NO synthase inhibitor, NG-nitro-l-arginine methyl ester (l-NAME). Exposure of snails to an ELF magnetic field (15 min, 60 Hz, 141 microT peak) also reduced the enkephalinase-induced antinociception. The inhibitory effects of the 60-Hz magnetic field were significantly reduced by the NO synthase inhibitor, l-NAME, and significantly enhanced by the NO releasing agent, SNP, at dosages which by themselves had no evident effects on nociceptive sensitivity. These results suggest that: (1) NO and NO synthase have antagonistic effects on opioid-induced analgesia in the snail, Cepaea and (2) the inhibitory effects of ELF magnetic fields on opioid analgesia involve alteration in NO and NO synthase activity.

Animals↗

PubMed1998

Parasitized female mice display reduced aversive responses to the odours of infected males.

The present study showed that parasites influence both the responses of uninfected females to males and the responses of female hosts to infected males. In female laboratory mice one of the consequences of exposure to the olfactory cues associated with an infected male was a reduction of the reactivity to a thermal surface, i.e. pain inhibition or analgaesia. Uninfected oestrous and non-oestrous female mice displayed marked analgaesic responses after exposure to the odours of males infected with either the enteric single-host nematode parasite, Heligmosomoides polygyrus, or the protozoan parasite, Eimeria vermiformis. The uninfected oestrous females distinguished between infected and physically stressed males, displaying a greater analgaesic response to the odours of infected males. These analgaesic responses and their anxiety/ fearfulness-associated behavioural correlates could elicit either a reduced interest in, or avoidance of, parasitized males by females. Oestrous female mice infected with H. polygyrus displayed a reduced analgaesic response to the odours of the infected males and differentially responded to the odours of males infected with either the same (H. polygyrus) or a different parasite (E. vermiformis). An exposure time of 1 min elicited minimal responses to the odours of males infected with the same parasite, H. polygyrus, and an attenuated, though significant, non-opioid peptide-mediated analgaesic response to males infected with E. vermiformis. An exposure time of 30 min elicited similar markedly reduced endogenous opioid peptide-mediated analgaesic responses to the odours of both of the categories of infected males. The responses to the odours of a stressed male were, however, unaffected by the parasitic infection. The reduced analgaesic responses of the parasitized females to the odours of infected males may involve either enhanced odour familiarity and responses to group odour templates and/or neuromodulatory shifts resulting in reduced fearfulness and potentially greater interest in the infected males.

Animals↗

PubMed1998

Plasma testosterone levels are related to various aspects of locomotor activity in wild-caught male meadow voles (Microtus pennsylvanicus).

The relationship between plasma testosterone levels and locomotor activity in wild-caught sexually mature male meadow voles (Microtus pennsylvanicus) was assessed in the laboratory. Several aspects of locomotor activity were monitored for 1 h on two consecutive days using the automated Digiscan activity monitoring system. Plasma testosterone levels were determined immediately following the second day of activity monitoring. Significant Pearson correlations were obtained between plasma testosterone levels and total distance traveled [r(10) = 0.55, p < 0.05] and amount of time spent in movement [r(10) - 0.55, p < 0.05] on the second day. The wild voles showed a reduction in activity levels from the first to the second day of activity monitoring, which is indicative of habituation to a novel environment. This study provides direct evidence for a significant correlation between laboratory measures of behavioral activity and plasma testosterone levels in a wild-caught rodent. These findings indicate that previous assessments of hormone-behavior relationships in laboratory-bred rodents are consistent with the relationship between hormones and behavior in wild rodents.

Activity Cycles↗

PubMed1998

Social learning of a food preference in male and female Mongolian gerbils is facilitated by the anxiolytic, chlordiazepoxide.

Social transmission of a food preference in Mongolian gerbils (Meriones unguiculatus) depends on the presence of a social bond between the interacting animals. An "observer" gerbil can acquire a preference for a novel food item from a familiar and, or related "demonstrator" animal. However, exposure to an unfamiliar and unrelated demonstrator gerbil does not lead to acquisition of a food preference, even though the extent of social interaction and likelihood of transmission of food information is unaffected. Likewise, individual preexposure to a novel food does not affect diet preference in individual animals. Here we show that oral, nongavage, administration of the benzodiazepine anxiolytic, chlordiazcpoxide (CDP, 2.5, 5, and 10 mg/kg) has significant dose-associated differential facilitatory effects on social learning in male and female gerbils, while having no significant effects on either individual learning or total food consumption. These results suggest that the CDP mediated reduction of the anxiety associated with the interactions between unfamiliar/unrelated gerbils facilitates social learning. These findings also rise the possibility of sex differences in socially related anxiety and the effects of CDP on social learning in gerbils.

Animals↗

PubMed1998

Analgesic effects of a specific pulsed magnetic field in the land snail, Cepaea nemoralis: consequences of repeated exposures, relations to tolerance and cross-tolerance with DPDPE.

It has been demonstrated previously that a short acute exposure to a specific extremely low frequency pulsed magnetic field (Cnp) can induce significant partly opioid-mediated analgesia in the land snail, Cepaea nemoralis. Here, this Cnp-induced analgesia is examined for the development of tolerance to daily repeated acute exposures of 15 or 30 min duration. Acute cross-tolerance to the delta opioid receptor directed agonist DPDPE, [D-Pen2, D-Pen5]enkephalin, was also found. Before (pre-exposure) and after (0, 15, 30 and 60 min) exposure to either a sham or Cnp magnetic field, snails were tested for an aversive reaction to a warmed surface (40 degrees C), and the latency time to the aversive reaction was recorded. Snails that were exposed to the Cnp showed a significant increase in the latency time (F1.55 = 2856.4; p < 0.001; Eta2 = 0.95), which may be interpreted as an induction of analgesia. During the daily (9 day) repeated acute exposures, the induction of analgesic response was significantly reduced, but not ablated. Altering the environmental conditions of the Cnp exposure restored a significant proportion of the partly developed tolerance, consistent with previous reports of environmental specificity in the development of opioid tolerance. These findings suggest that the partial development of tolerance to the opioid-mediated portion of Cnp-induced analgesia may be countered by altering the specific environmental Cnp exposure conditions.

Analgesia↗

PubMed1998

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↗

PubMed1998

Analgesic responses of male mice exposed to the odors of parasitized females: effects of male sexual experience and infection status.

The present study shows that parasites influence both the responses of males to infected females and the responses of male hosts to females. Male mice exposed for 30 min to the odors of females infected with the nematode parasite Heligmosomoides polygyrus displayed a naloxone-sensitive, opioid-mediated analgesia, whereas males exposed for 1 min showed a shorter duration and lower amplitude naloxone-insensitive "nonopioid" analgesia that involved serotoninergic (5-HT) and excitatory amino acid (N-methyl-D-aspartate [NMDA] receptor) systems. The male mice distinguished between the odors of infected and physically stressed females, displaying greater analgesia after exposure to the odors of infected than stressed females. The analgesic responses to the odors of infected females were also affected by the males' prior sexual experience; sexually experienced males exhibited significantly greater analgesia than sexually naive males. In contrast, male mice infected with H. polygyrus failed to show a nonopioid analgesia after exposure to the odors of infected females and displayed a markedly lower level of opioid analgesia than uninfected mice. These results show that male mice can discriminate between the odors of parasitized and nonparasitized females and find the odors of parasitized estrous females aversive.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1997

Sex differences in N-methyl-D-aspartate involvement in kappa opioid and non-opioid predator-induced analgesia in mice.

There are suggestions of sex differences in N-methyl-D-aspartate (NMDA) receptor system involvement in the mediation of analgesia. The present study examined the effects of the specific, competitive NMDA antagonist, NPC 12626, on the nociceptive (50 degrees C hot plate) responses of reproductive male and female laboratory mice exposed to (i) an ethologically relevant aversive stimulus, the odor of a predator and (ii) administration of the kappa opiate agonist, U69,593. A 30-s exposure to 2-propylithietane, the major component of weasel odor, elicited a 'non-opioid' analgesia that was in both sexes insensitive to naloxone and the kappa opiate antagonist nor-binaltorphimine. In male mice this non-opioid analgesia was antagonized by NPC 1262, while in reproductive females the predator-induced analgesia was insensitive to NPC 12626. Similarly, NPC 12626 attenuated the analgesic effects of the kappa opiate agonist, U69,593, in male mice while having no significant effects on the equivalent levels of kappa opiate analgesia in females. These results show that there are sex differences in NMDA involvement in the expression and, or mediation of both non-opioid stress-induced and kappa opiate-mediated analgesia.

Analgesia↗

PubMed1997

Opioid and non-opioid NMDA-mediated predator-induced analgesia in mice and the effects of parasitic infection.

The present study examined the nociceptive responses (50 degrees C, hot-plate) of uninfected and subclinically parasitized male mice exposed to the odor of a predator, an ecologically relevant threatening stimulus. In uninfected mice a 15-min exposure to 2-propylthietane, the major component of weasel odor, induced a naloxone-reversible opioid analgesia. A 30-s exposure elicited a shorter duration and lower amplitude 'non-opioid' analgesia that was insensitive to naloxone, partially sensitive to either the serotonin-1A (5-HT1A) agonist, 8-OH-DPAT, or the GABAA antagonist, bicuculline, and blocked by the competitive N-methyl-D-aspartate (NMDA) antagonist, NPC 12626. In contrast, mice chronically (25 days) and subclinically infected with the murine nematode, Heligmosomoides polygyrus, failed to show a significant non-opioid analgesia and displayed a markedly lower level of opioid analgesia than uninfected mice. These results suggest that NMDA receptor mechanisms are potently associated with the expression of the analgesia arising from exposure to the naturally aversive stimulus of predator odor. These findings also demonstrate that parasites, and likely other subchronic infections, can have a significant impact on the display of opioid and non-opioid stress-induced analgesia arising from exposure to the ethologically relevant stimulus of predator odor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1997

Antinociceptive effects of a pulsed magnetic field in the land snail, Cepaea nemoralis.

Pulsed magnetic fields (patent pending) consisting of approximately 100 microT (peak), frequency modulated, extremely low frequency magnetic fields (ELFMF) were shown to induce a significant degree of antinociception ('analgesia') in the land snail Cepaea nemoralis. Fifteen minute exposures to a specific magnetic field both increased enkephalinase inhibitor induced opioid analgesia and induced analgesia in untreated snails. Injection of the prototypic opioid antagonist naloxone, attenuated, but did not completely block, the pulsed magnetic field induced analgesia. Two other pulsed waveform designs failed to induce analgesia in untreated snails. These findings suggest that specific magnetic field exposure designs may be tailored to produce significant behavioral effects including, but certainly not limited to, the induction of analgesia.

Analgesia↗

PubMed1997

Light-dependent and -independent behavioral effects of extremely low frequency magnetic fields in a land snail are consistent with a parametric resonance mechanism.

Exposure to extremely low frequency (ELF) magnetic fields has been shown to attenuate endogenous opioid peptide mediated antinociception or "analgaesia" in the terrestrial pulmonate snail, Cepaea nemoralis. Here we examine the roles of light in determining this effect and address the mechanisms associated with mediating the effects of the ELF magnetic fields in both the presence and absence of light. Specifically, we consider whether the magnetic field effects involve an indirect induced electric current mechanism or a direct effect such as a parametric resonance mechanism (PRM). We exposed snails in both the presence and absence of light at three different frequencies (30, 60, and 120 Hz) with static field values (BDC) and ELF magnetic field amplitude (peak) and direction (BAC) set according to the predictions of the PRM for Ca2+. Analgaesia was induced in snails by injecting them with an enkephalinase inhibitor, which augments endogenous opioid (enkephalin) activity. We found that the magnetic field exposure reduced this opioid-induced analgaesia significantly more if the exposure occurred in the presence rather than the absence of light. However, the percentage reduction in analgaesia in both the presence and absence of light was not dependent on the ELF frequency. This finding suggests that in both the presence and the absence of light the effect of the ELF magnetic field was mediated by a direct magnetic field detection mechanism such as the PRM rather than an induced current mechanism.

Animals↗