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Biomedical subjects

M Kavaliers

Publications and source records attributed to M Kavaliers.

At least 91 records · Page 5Linked to original sources

Repeated naloxone treatments and exposures to weak 60-Hz magnetic fields have 'analgesic' effects in snails.

Results of studies with rodents have shown that animals repeatedly injected with the opioid antagonist, naloxone, acquire a hypoalgesic response to thermal nociceptive stimuli. The present study revealed a similar response in the terrestrial pulmonate snail, Cepaea nemoralis. Snails receiving daily injections of naloxone followed by measurements of thermal nociceptive sensitivity also developed hypoalgesia. Daily brief (30-min) exposures to a weak 60-Hz magnetic field (1.0 gauss or 0.1 mT), which acutely antagonize opioid-mediated nociception and antinociception in a manner comparable to that of naloxone, also led to the expression of a hypoalgesic responses. This suggests that opioid antagonist-induced thermal hypoalgesia may be a basic feature of opioid systems. This naloxone- and magnetic field-induced 'analgesia' is consistent with either a facilitation of aversive thermal conditioning and or antagonism of the excitatory, hyperalgesic effects of low levels of endogenous opioids.

Analgesia↗

Predator-induced opioid and non-opioid mediated analgesia in young meadow voles: sex differences and developmental changes.

The present study examined developmental changes in the nociceptive responses of male and female meadow voles, Microtus pennsylvanicus, exposed to a garter snake, a natural predator of young voles. After 15 min of exposure to the presence of a garter snake, neonatal-juvenile voles (5-20 days of age) displayed naloxone (1.0 mg/kg)-sensitive opioid mediated analgesic responses, while after a brief 30-s exposure to the snake, voles displayed a higher amplitude, non-opioid analgesia that was insensitive to naloxone and blocked by the serotonin-1A (5-HT1A) agonist, 8-hydroxy-2-(di-n-propylamino)tetralin. The levels of opioid and non-opioid mediated analgesia declined during development as the threat presented by the snake decreased. Young female voles also displayed a significantly greater non-opioid, 5-HT1A sensitive analgesia than males, with no significant sex differences in the lower amplitude opioid analgesia. These results indicate that young (neonatal) meadow voles that are exposed to a naturally threatening stimulus display sexually dimorphic analgesic responses. These findings also illustrate the need to consider the ecological context when examining environmentally-induced analgesia.

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

Neuropeptide FF (FLQPQRFamide) and IgG from neuropeptide FF antiserum affect spatial learning in mice.

There is evidence indicating that the mammalian octapeptide FLQPQRFamide (F8Fa or neuropeptide FF, NPFF) is an endogenous modulator ('anti-opioid') of opioid systems. There is also substantial evidence implicating opioid systems in the mediation of spatial learning and memory. In the present study determinations were made of the effects of NPFF and IgG from antiserum against NPFF on the spatial performance of male mice in a water maze task, whereby over one day in six blocks of four trials the animals had to acquire the location of a submerged hidden platform using distal visual cues. Pretraining intracerebroventricular (i.c.v.) injection of NPFF-IgG, impaired spatial acquisition and retention, while i.c.v. administration of 1.0 microgram of NPFF marginally improved, and 10 micrograms of NPFF significantly reduced spatial acquisition. These results suggest that NPFF may have a modulatory influence on spatial acquisition.

Amino Acid Sequence↗

Sex differences in the antinociceptive effects of the enkephalinase inhibitor, SCH 34826.

The effects of endogenous opioid peptides are limited by proteolytic enzymes such as endopeptidase 24.11 ("enkephalinase"), which cleaves the Gly-Phe bonds in Met- and Leu-enkephalin. SCH 34826 [(S)-N-[n-[1-[(2,2-dimethyl-1,3-dioxolan-4- yl)methoxy]carbonyl]-2-phenylethyl]-L-phenyl-alanine-B-alanine] is a potent, highly specific, enkephalinase inhibitor that has marked analgesic effects in laboratory rodents. The present study compared the effects of SCH 34826 on nociception and restraint stress-induced opioid analgesia in reproductive adult male and female deer mice, Peromyscus maniculatus. SCH 34826 had significantly greater antinociceptive actions and facilitatory effects on stress-induced analgesia in male than female mice. These antinociceptive effects of SCH 34826 were reduced by the general opioid antagonist naloxone and completely blocked by the specific delta opioid receptor antagonist, ICI 174,864, and nonsignificantly affected by the mu and kappa opioid receptor antagonists, beta-funaltrexamine and nor-binaltorphimine, respectively. These results show that there are sex differences in the effects of the enkephalinase inhibitor, SCH 34826, on opioid-mediated antinociception and that these sex differences are associated with delta opioid mechanisms.

Analgesia↗

Evidence for involvement of endogenous opioid peptides in altered nociceptive responses of mice infected with Eimeria vermiformis.

Parasite modification of host behavior is a well established phenomenon; however, little is known about the modulatory mechanisms regulating such effects. This study examined the relationship between Eimeria vermiformis infection, nociceptive responses, and endogenous opioid peptide activity in male RML mice. Infected mice displayed increases in centrally mediated antinociceptive responses (i.e., analgesia, measured as the latency of a foot-lifting response to a 50 C surface) throughout the prepatent period. The level of analgesia declined following onset of patency on day 8 postinfection (PI). Opioids were implicated in the increased antinociceptive response of the infected mice as the response was blocked by administration of a prototypic opiate antagonist, naloxone (1.0 mg/kg), on day 7 PI when maximum levels of analgesia were noted. This indicates that the analgesia evident in the parasitized mice was associated with increased opioid activity. Analgesia is one of a variety of behaviors influenced by changes in opioid activity, thus these observations provide further support for the contention that other parasite-induced alterations in host behavior may, in part, be the result of alterations in the activity of opioid modulatory systems.

Animals↗

Sodium arsanilate-induced vestibular dysfunction in meadow voles (Microtus pennsylvanicus): effects on posture, spontaneous locomotor activity and swimming behavior.

Vestibular dysfunction was chemically induced in male meadow voles (Microtus pennsylvanicus) by intratympanic injections (30 mg per side) of sodium arsanilate (atoxyl). The control group received intratympanic injections of isotonic saline. After a one-week recovery period the voles were behaviorally assayed for integrity of their labyrinthine systems. All subjects were tested for the presence of the air-righting reflex and body rotation-induced nystagmus. Three weeks later a multivariate assessment of spontaneous motor activity of the voles was carried out in the automated Digiscan Activity Monitor. In addition, the swimming behavior of the voles was examined. Voles with vestibular dysfunction exhibited pronounced postural abnormalities (head dorsiflexion), were not able to swim with their nose above the water for a 1 min test period, and displayed disorientation and thrashing movements. In the Digiscan activity test the atoxyl-treated voles displayed significantly more activity in the horizontal measures (Ps less than 0.01), including greater distance travelled per movement and greater speed of movements, relative to the control animals. The labyrinthectomized group also spent significantly (P less than 0.05) less time in vertical movements and exhibited significantly more time in stereotypic behavior (P less than 0.01), relative to controls. Atoxyl-treated voles also showed significantly less thigmotaxis (wall-hugging) than the control animals (P less than 0.01). In general, changes in spontaneous behavior observed in the sodium arsanilate-treated voles were consistent with the presence of postural and balance abnormalities and a redirecting of exploratory vertical movements toward horizontal locomotion to the extent that these animals were clearly hyperactive in this dimension. The multivariate behavioral assessment available in the Digiscan Activity Monitoring system, thus seems to be especially useful in the examination of behavioral components affected by vestibular dysfunction.

Animals↗

Exposure to the scent of male mice infected with the protozoan parasite, Eimeria vermiformis, induces opioid- and nonopioid-mediated analgesia in female mice.

The present study examined the nociceptive responses of female mice exposed to the scent (soiled cage bedding) of male mice infected with the protozoan parasite, Eimeria vermiformis. A 30-min exposure to the odors of a parasitized male induced naloxone (1.0 mg/kg)-sensitive opioid-mediated analgesia in female mice, whereas a brief 1-min exposure to these odors resulted in a lower amplitude, relatively short, nonopioid analgesia that was insensitive to naloxone and blocked by the serotonin-1A (5-HT1A), agonist, 8-OH-DPAT. Exposure to the odors of nonparasitized males had no significant effects on the nociceptive responses of female mice. These results indicate that female mice are able to distinguish between the odors of parasitized and nonparasitized male mice, and that female mice display both opioid- and nonopioid-mediated aversive responses to the odor cues associated with the parasitized males. The implications of these findings for parasite-based mate choice are discussed.

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

Evidence for activation of endogenous opioid systems in mice following short exposure to stable flies.

Biting flies influence both physiology and behaviour of domestic and wild animals. This study demonstrates that brief (30 min) exposure of male and female mice to stable flies leads to significant increases in nociceptive responses, indicative of the induction of analgesia. The biting fly-induced analgesia was mediated by endogenous opioid systems as it was blocked by the prototypic opiate antagonist naloxone. Exposure for 30 min to the bedding of biting fly-exposed mice also induced significant opioid mediated analgesic responses in mice. Exposure to either house flies or the bedding of house fly-exposed mice had no significant effects on nociception. These results indicate that brief exposure to either stable flies, or to olfactory cues associated with mice exposed to stable flies, activates endogenous opioid systems leading to the induction of analgesia and likely other opioid mediated behavioural and physiological stress responses. These results suggest the involvement of endogenous opioid systems in the mediation of the behavioural and physiological consequences of biting fly exposure in domestic and wild animals.

Animals↗

Sex differences in opioid and non-opioid mediated predator-induced analgesia in mice.

The present study compared the nociceptive responses of male and female mice exposed to a predator, an ecologically relevant threatening stimulus. After 15 min of exposure to the presence of an experienced predatory cat, mice displayed a naloxone (1.0 mg/kg)-sensitive opioid mediated analgesic response, while after a brief 30-s exposure to the cat mice displayed a lower amplitude, relatively brief, non-opioid analgesia that was insensitive to naloxone and blocked by the serotonin-1A (5-HT1A) agonist, 8-hydroxy-2-(di-n-propylamino)tetralin. Male mice displayed a significantly greater opioid mediated predator-induced analgesia than females, whereas female mice showed a significantly greater non-opioid, 5-HT1A sensitive, analgesia than males. These results indicate that there are significant sex differences in both the opioid and non-opioid analgesic responses arising from exposure to a natural aversive stimulus.

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

Evidence for the involvement of protein kinase C in the modulation of morphine-induced 'analgesia' and the inhibitory effects of exposure to 60-Hz magnetic fields in the snail, Cepaea nemoralis.

There is substantial evidence that magnetic fields can reduce opiate-induced analgesia, with alterations in calcium channel function and/or calcium ion flux being implicated in the mediation of these inhibitory effects. The present experiments were designed to examine the effects of protein kinase C (PKC), a calcium/diacylglycerol/phospholipid-dependent protein kinase, on opiate-induced analgesia and its involvement in mediating the inhibitory effects of exposure to magnetic fields. We observed that morphine-induced antinociception, or 'analgesia', in the land snail, Cepaea nemoralis, as measured by the enhanced latency of response to a thermal (38.5 degrees C) stimulus, was reduced in dose-related manner by the PKC activator, SC-9. Exposure of snails for 2 h to a low intensity (1.0 gauss rms) 60-Hz magnetic field also reduced morphine-induced analgesia. The inhibitory effects of the 60-Hz magnetic field on morphine-induced analgesia were significantly reduced by the PKC inhibitors, H-7 and H-9, and significantly enhanced by the PKC activator, SC-9. The non-specific protein kinase inhibitor, HA-1004, and the preferential calmodulin inhibitor, W-7, had no significant effects on either morphine-induced analgesia or the inhibitory actions of exposure to the magnetic fields. These results suggest that: (1) PKC has antagonistic effects on opiate-mediated analgesia in the snail, Cepaea, and (2) that the inhibitory effects of magnetic fields on opiate-induced analgesia involve alterations in PKC.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Inhibitory effects of 60-Hz magnetic fields on opiate-induced "analgesia" in the land snail, Cepaea nemoralis, under natural conditions.

There is accumulating laboratory evidence that magnetic fields can affect a variety of opioid-mediated behavioral and physiological functions in both vertebrates and invertebrates. The present study examined the effects of various durations (0.50, 1.0 and 2.0 h) of exposure to a low intensity (1.0 gauss rms) 60-Hz magnetic field on opioid-mediated aversive thermal ("nociceptive") responses and morphine-induced "analgesia" in the land snail, Cepaea nemoralis, under natural environmental conditions. Exposure to the powerline-related 60-Hz magnetic fields significantly attenuated morphine-induced analgesia and the basal nociceptive responses of Cepaea, with the degree of attenuation being related to the duration of exposure to the magnetic fields. These results with Cepaea show that 60-Hz magnetic fields can affect opioid-mediated behavioral responses outside the laboratory under natural environmental conditions.

Animals↗

Modifications of social conflict-induced analgesic and activity responses in male mice receiving chronic opioid agonist and antagonist treatments.

This study examined the effects of chronic (7 day) administrations of opioid agonists, via osmotic minipumps (20 micrograms/microliters/h, or 2 mg/kg/h for each agent) on: 1) nociception and activity, and 2) the analgesic and locomotor responses of subordinate male mice experiencing social conflict (aggression without defeat) and defeat in a "resident-intruder" paradigm. Chronic infusion of the mu opioid antagonist, naltrexone, resulted in a hypoanalgesic response and a decrease in basal locomotor activity on days 3-7 postimplantation which returned to the basal levels of saline-implanted control mice after termination of the infusions on day 9. Naltrexone reduced defeat-induced analgesia on the second day after implantation, but had no consistent effects on analgesia on test days 6 and 9 or on the aggression-induced (nondefeat) analgesia and increases in activity. The delta opioid antagonist ICI-154, 129, while having no significant effects on basal nociception or locomotor activity, augmented nondefeat-induced analgesia (day 2) and reduced the defeat-induced increases in activity (days 2 and 6). The mu agonist, levorphanol, resulted in a significant analgesia on the first two days after infusion, followed by the development of tolerance to the analgesic effects over days 3-7. On day 9, a hypoanalgesic response indicative of withdrawal was evident. Levorphanol also induced a marked decrease in locomotor activity over days 3-7 postimplantation, with no evidence of the development of tolerance or withdrawal following termination of infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Inhibitory influences of mammalian FMRFamide (Phe-Met-Arg-Phe-amide)-related peptides on nociception and morphine- and stress-induced analgesia in mice.

The effects of two endogenous mammalian FMRFamide (Phe-Met-Arg-Phe-NH2)-related peptides, an octapeptide F8Fa (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) and an octadecapeptide A18Fa (Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala-Ala-Pro-Gln-Arg-Phe -NH2) on morphine- and restraint stress-induced analgesia and basal nociceptive sensitivity, as measured by the latency of a foot-lifting response to a warmed surface, were examined in male mice. Intracerebroventricular (i.c.v.) administrations of F8Fa and A18Fa (0.10-10 micrograms) during the day-time significantly reduced morphine (10 mg/kg) and restraint-induced analgesia at 30 min after administration, with F8Fa having a greater inhibitory effect than A18Fa. At night during the dark period i.c.v. F8Fa also significantly reduced the elevated nocturnal thermal response latency, while not affecting the shorter day-time nociceptive responses. Peripheral administrations of the prototypic opiate antagonist, naloxone (1.0 mg/kg), had similar inhibitory effects on morphine- and stress-induced analgesia, and the day-night rhythm of nociceptive sensitivity. These results indicate that F8Fa and A18Fa are involved in the modulation of opioid analgesia and suggest that these endogenous FMRFamide-related peptides may be associated with the expression of the day-night rhythm of opioid-mediated nociceptive sensitivity.

Amino Acid Sequence↗

Magnetic resonance imaging increases the blood-brain barrier permeability to 153-gadolinium diethylenetriaminepentaacetic acid in rats.

In a qualitative electron microscopy study we initially reported that exposure of rats to a standard clinical magnetic resonance imaging (MRI) procedure temporarily increased the blood-brain barrier (BBB) permeability to horseradish peroxidase. In this study, we quantitatively support our initial finding. Rats were injected intracardially with radio-labelled diethylenetriaminepentaacetic acid [( 153Gd]DTPA) in the middle of two sequential 23.2 min MRI exposures. Exposed rats (n = 21) showed significantly greater (29%, P = 0.006) retention of [153 Gd]DTPA than sham-exposed rats (n = 22) 1 h after the end of the last 23.2 min exposure. These findings suggest that magnetic fields may alter BBB permeability.

Animals↗

Increased mortality in land snails (Cepaea nemoralis) exposed to powerline (60-Hz) magnetic fields and effects of the light-dark cycle.

The effects of various durations (0.5, 2, 12, 48, or 120 h) of day- and night-time exposures to a 1.0 gauss (rms) 60-Hz magnetic field or sham field on mortality levels in the nocturnally-crepuscularly active land snail, Cepaea nemoralis, were examined. These snails were injected with morphine or saline vehicle and tested for reaction to an aversive thermal stimulus as part of another study. Mortality levels were monitored over a 2-week period following the initial exposure to the fields and were shown not to be differentially affected by the drug injection procedures. Mortality levels increased linearly as a function of increased length of exposure to the magnetic fields (P less than 0.001) but not when exposed to the sham fields. As well, night-time exposures resulted in greater mortality levels than day-time exposures (P less than 0.025). These results indicate that day-night rhythms are important in determining the magnitude of the magnetic field exposure effect. It is speculated that the magnetic fields may disrupt endogenous opioid- and calcium-modulated homeostatic mechanisms and augment stress effects, modifying a variety of systems including immunocompetence.

Animals↗

Day-night rhythms in the inhibitory effects of 60 Hz magnetic fields on opiate-mediated 'analgesic' behaviors of the land snail, Cepaea nemoralis.

There is accumulating evidence that magnetic fields can affect a variety of opioid-mediated behavioral and physiological functions. The present experiments were designed to examine the effects of various durations of day- and night-time exposures to low intensity (1.0 gauss rms) 60 Hz magnetic fields on light (L) and dark (D) period opioid-mediated aversive thermal ('nociceptive') responses and morphine-induced 'analgesia' in the nocturnally-crepuscularly active land snail, Cepaea nemoralis. The snails displayed a LD rhythm in the latency of their aversive (40 degrees C) thermal (nociceptive) responses, showing a significantly greater response latency at night than during the day. Administration of morphine (10 mg/kg/2.0 microliters) elicited significant increases in the thermal response latencies indicative of the induction of analgesia. The snails displayed a significantly greater analgesic response at night than during the day. Exposure (0.50, 2, 12, 48 or 120 h in L or D) to the 60 Hz fields reduced morphine-induced analgesia in both the L and D periods, with the magnetic stimuli having significantly greater inhibitory effects in the D period. The magnetic fields also significantly attenuated the level of the dark period basal nociceptive response latencies, while not affecting the light period responses. In both the L and D periods the degree of attenuation of the analgesic and nociceptive response latencies was related to the duration of exposure to the 60 Hz magnetic fields.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗

Developmental changes in opiate-induced analgesia in deer mice: sex and population differences.

We examined developmental changes in nociception and mu (morphine) and kappa (U-50,488) opiate-induced analgesia in male and female deer mice of two different populations; Peromyscus maniculatus artemisiae from a mainland region and P. m. angustus from a small island. Both populations displayed significant developmental changes in nociception and morphine (10 mg/kg) and U-50,488 (10 mg/kg)-induced analgesia. Basal thermal response latencies (nociceptive responses) and the levels of mu and kappa opiate-induced analgesia increased over 14-35 days of age, with maximum analgesic responses in adults (35+ days of age). In both of the populations, young (neonatal-weaning) male mice displayed significantly higher thermal response latencies and greater levels of naloxone (1.0 mg/kg) antagonized opiate-induced analgesia than young females. There were also population differences in the levels of analgesia, the insular mice displaying greater mu and lower kappa opiate-induced analgesic responses than the mainland animals. The population differences in mu and kappa opiate-induced analgesia were evident in young and adult mice of both sexes. These results show that there are significant sex and population differences in nociception and opiate-induced analgesia in young (neonatal-weaning) and adult deer mice.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗