Search PubMed⌕ Search

Biomedical subjects

M Kavaliers

Publications and source records attributed to M Kavaliers.

At least 127 records · Page 7Linked to original sources

Exposure to novel odors induces opioid-mediated analgesia in the land snail, Cepaea nemoralis.

Land snails, Cepaea nemoralis, that were exposed for 1-30 min to a novel odor of either peppermint extract or vegetable juice concentrate displayed an increase in the latency of their nociceptive response to an aversive thermal stimulus (40 degrees C, hot-plate). This "analgesic" response, which entailed the elevation of the fully extended foot in hydrated snails, was evident directly after exposure to the novel chemostimuli and lasted for 15-30 min. This novelty-induced analgesia was blocked by the exogenous opiate antagonist naloxone. Analgesia was not observed in snails that were exposed to the same olfactory cue 4 or 24 h later, but was evident when the alternate novel odor (peppermint or vegetable juice) was presented. However, a significant analgesia was displayed by snails that were reexposed to their initial olfactory stimulus after 48-72 h. These findings indicate that exposure to a novel olfactory stimulus can activate endogenous opioid systems and induce an analgesic response in mollusks.

Animals↗

Novelty-induced opioid analgesia in deer mice (Peromyscus maniculatus): sex and population differences.

Exposure to a new environment elicited significant, naloxone (1.0 mg/kg) reversible analgesic responses in three different populations of deer mice; Peromyscus maniculatus artemisiae from the mainland, and P. m. angustus and P. m. triangularis from small marine islands. In all cases male deer mice displayed significantly greater levels of analgesia than females. In addition, the levels of analgesia were significantly greater in the insular than in the mainland populations. These results indicate that there are substantial sex and population differences in the novelty-induced analgesia displayed by natural and laboratory populations of deer mice.

Analgesia↗

Stress-induced opioid analgesia and activity in deer mice: sex and population differences.

We compared restraint stress-induced opioid, analgesic and locomotory responses of 4 different populations of male and female deer mice, Peromyscus maniculatus artemisiae and P. m. nebrascensis from mainlands, and P. m. angustus and P. m. triangularis from small islands. All of the deer mice displayed immobilization-induced analgesia which was blocked by the prototypical mu-opiate antagonist, naloxone (1.0 mg/kg). In all of the populations males displayed significantly greater levels of analgesia than females. In addition, the levels of opioid-induced analgesia were significantly greater in the insular than in the mainland male and female deer mice. Restraint also induced significant increases in the locomotor activity of the mainland deer mice, while significantly decreasing the activity of the insular animals. Males displayed significantly greater stress-induced changes in locomotor activity than did females. The stress-induced increases in activity were blocked by the delta-opiate antagonist, ICI 154, 129 (10 mg/kg), while the decreases in activity were inhibited by naloxone. These results demonstrate that there are marked sex and population differences in the stress-induced, opioid-mediated responses of deer mice. These 'pharmaco-ecological' findings also suggest that the island-mainland population differences in behavioral responses and ecological characteristics may, in part, be related to differences in the activity of mu-, delta- and possibly other opioid systems.

Animals↗

Morphine-induced analgesia and exposure to low-intensity 60-Hz magnetic fields: inhibition of nocturnal analgesia in mice is a function of magnetic field intensity.

In 2 experiments male CF-1 mice were exposed for 60 min, during the mid-dark period of the day-night cycle, to low-intensity (0.5-1.5 gauss, rms) 60-Hz magnetic fields and then tested for levels of analgesia induced by morphine (10 mg/kg) injections. The magnetic field exposures inhibited the degree of morphine-induced analgesia in a field intensity-dependent manner in both experiments (P less than 0.01) with the largest inhibitory effect after exposure to the 1.5-gauss field. Analysis of the combined data from the two experiments revealed a significant (P less than 0.001) linear relationship between level of analgesia and magnetic field intensity. Thus, these data demonstrated a functional relationship between the behavioral effects of morphine in mice and the strength of the 60-Hz magnetic field. Possible mechanisms underlying these effects are discussed.

Analgesia↗

Calcium channel blockers inhibit the antagonistic effects of Phe-Met-Arg-Phe-amide (FMRFamide) on morphine- and stress-induced analgesia in mice.

Determinations were made of the effects of the calcium channel blockers, nifedipine and verapamil, on the antagonistic effects of FMRFamide (Phe-Met-Arg-Phe-NH2) and naloxone on morphine- and immobilization-induced opioid analgesia in mice. Intraperitoneal (i.p.) administrations of the calcium channel antagonists significantly reduced the inhibitory effects of intracerebroventricular (i.c.v.) FMRFamide, but had no effects on i.p. or i.c.v. naloxone-mediated inhibition of either morphine- or immobilization-induced analgesia. These results suggest that the antagonistic effects of FMRFamide, (or other endogenous FMRFamide-like peptides) on both opiate- and opioid-mediated analgesia in mice may involve alterations in the functioning of calcium channels.

Animals↗

Analgesic effects of the progesterone metabolite, 3 alpha-hydroxy-5 alpha-pregnan-20-one, and possible modes of action in mice.

The effects of intracerebroventricular (i.c.v.) administrations of the progesterone metabolite, 3 alpha-hydroxy-5 alpha-pregnan-20-one (3A5P), on the nociceptive responses of male mice were examined. 3A5P elicited significant, dose-dependent (0.001-1.0 microgram) analgesia for 90-120 min after administration. These effects of 3A5P were significantly more potent than those of progesterone. The stereoisomer, 3 beta-hydroxy-5 alpha-pregnan-20 one (3B5P), failed to affect the nociceptive responses, indicating that the analgesic effect of 3A5P is stereospecific. The analgesic effects of 3A5P were blocked by peripheral administrations of the GABA antagonists, bicuculline and picrotoxin, and reduced by both the opiate and benzodiazepine antagonists, naloxone and Ro 15-788, respectively. The calcium channel antagonists, nifedipine and verapamil, enhanced 3A5P-induced analgesia but had no evident effects on the actions of 3B5P. These results suggest that the central analgesic effects of the progesterone metabolite, 3A5P, may arise via mechanisms involving calcium channels, the GABA-benzodiazepine-chloride complex and endogenous opioid systems.

Analgesics↗

Evidence for opioid and non-opioid forms of stress-induced analgesia in the snail, Cepaea nemoralis.

Exposure to either cold or warm stress increased the thermal nociceptive thresholds of the terrestrial snail, Cepaea nemoralis. The warm stress-induced 'analgesia' was blocked by the prototypic opiate antagonist, naloxone, and the delta-opiate antagonist, ICI 154,129, and was suppressed by a 24-h pretreatment with the irreversible opiate antagonist, beta-funaltrexamine (B-FNA). In contrast, cold stress-induced analgesia was unaffected by either naloxone, ICI 154,129 or B-FNA. These results indicate that this mollusc displays both opioid and non-opioid forms of stress-induced analgesia in a manner analogous to that reported for mammals. These findings suggest an early evolutionary development and phylogenetic continuity of opioid and non-opioid mediated stress responses to aversive environmental stimuli.

Animals↗

Magnetic resonance imaging temporarily alters blood-brain barrier permeability in the rat.

Exposure to a short (23.2 min) standard clinical magnetic resonance imaging (MRI) procedure elicits a temporary dysfunction of the blood-brain barrier in rats. Monitoring of the increased permeability of rat brain frontal cortex microvessels with the protein tracer horseradish peroxidase and freeze-fracture electron microscopy, revealed an amplified vesicle-mediated transport of tracer across the microvessel endothelium to the albuminal basal lamina and extracellular compartment of the brain parenchyma. Recovery of normal blood-brain function, as evidenced by exclusion of protein tracer from subendothelial basal lamina and neuropil extracellular milieu, was complete 15-30 min following cessation of the MRI exposure. These findings raise the possibility that exposure to clinical MRI procedures may also temporarily alter central blood-brain permeability in human subjects.

Animals↗

Stimulatory influences of calcium channel antagonists on stress-induced opioid analgesia and locomotor activity.

The effects of the calcium channel antagonists diltiazem, nifedipine and the calcium channel agonist, BAY K 8644, on immobilization-induced opioid analgesia and locomotor activity were examined in CF-1 and C57BL strains of mice, respectively. The calcium channel antagonists enhanced the experimenatlly induced analgesia and activity, whereas the agonist reduced these responses. In addition, the calcium channel antagonists augmented, while the agonist attenuated, the analgesic effects of the specific mu and delta opioid agonists, DAGO and [D-Pen2,D-Pen5]-enkephalin (DPDPE), respectively. These results indicate that calcium channel antagonists have facilitatory and/or modulatory effects on the behavioral and physiological consequences of endogenous mu and delta opioid activity.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Opioid involvement in the control of feeding in an insect, the American cockroach.

Administration of the kappa opiate agonist, U-50,488H (0.10-10 mg/kg), produced over three hours a significant dose-dependent increase in the ingestive responses of free feeding American cockroaches, Periplaneta americana. These effects could be decreased by the opiate antagonist, naloxone (1.0 mg/kg), with naloxone by itself blocking the augmented feeding responses of food-deprived cockroaches. The mu opiate agonist, morphine (1.0-20 mg/kg) caused a significant dose-dependent and naloxone-reversible increase in the locomotory activity of cockroaches. These results suggest that opioid systems may be involved in the control of the feeding in cockroaches in a manner analogous to that proposed for vertebrates.

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

Aggression and defeat-induced opioid analgesia displayed by mice are modified by calcium channel antagonists and agonists.

The effects of the calcium channel antagonists diltiazem, nifedipine and verapamil and the calcium channel agonist, BAY K 8644, on offensive and defensive aggression and defeat-induced opioid analgesia were examined in male mice in resident-intruder interactions. The calcium channel antagonists decreased and the agonist increased the aggressive behaviors displayed by the mice. In addition, the calcium channel antagonists augmented, while the agonist attenuated defeat-induced analgesia displayed by the intruder mice. These results suggest that calcium channel antagonists have inhibitory influences on aggressive behavior and may facilitate endogenous opioid activity.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Calcium channel involvement in magnetic field inhibition of morphine-induced analgesia.

An exposure for 60 min to a weak 0.5 Hz rotating magnetic field significantly reduced the day-time analgesic effects of morphine in male mice. The dihydropyridine (DHP) calcium channel antagonists diltiazem and nifedipine and the non-DHP antagonist verapamil, as well as the inorganic calcium channel blockers, La3+ and Co2+, differentially reduced, while the DHP calcium channel agonist, BAY K 8644, enhanced the inhibitory effects of the magnetic stimuli. In a similar manner, though to a lesser degree, the calcium channel antagonists and agonist, increased and decreased, respectively, the inhibitory effects of intracerebroventricular administrations of Ca2+ on morphine-induced analgesia. The calcium channel antagonists and agonists had no significant effects on naloxone-mediated reductions of morphine-induced analgesia. These results suggest that exposure to magnetic stimuli affects the functioning of calcium channels and the distribution of calcium ions, thereby, altering the effects of opiates.

Animals↗

Sex differences in magnetic field inhibition of morphine-induced responses of wild deer mice, Peromyscus maniculatus triangularis.

An exposure for 60 min to a 0.5 Hz weak rotating magnetic field (1.5-90 G) reduced the day-time locomotory and analgesic effects of morphine (10 mg/kg) in a wild population of deer mice. Peromyscus maniculatus triangularis. Females displayed significantly lower levels of morphine-induced responses and sensitivity to the inhibitory effects of the magnetic fields than did the males. These responses indicate that there are sex differences in the effects of weak magnetic fields on the opiate-mediated responses of a wild rodent, with males being more responsive to the magnetic stimuli than females.

Analgesia↗

Sex and day-night differences in opiate-induced responses of insular wild deer mice, Peromyscus maniculatus triangularis.

We examined the effects of mu and kappa opiate agonists on the day- and night-time nociceptive, locomotory and ingestive behaviors of an island population of wild male and female deer mice, Peromyscus maniculatus triangularis. The prototypical mu opiate agonist, morphine, had significant analgesic and locomotory effects, which were blocked by naloxone, and the specific delta opiate antagonist, ICI 154,129, respectively. The specific kappa opiate agonist, U-50,488, had significant analgesic actions and inhibitory effects on locomotor activity, as well as stimulating feeding. Significant day-night variations occurred in the analgesic and activity responses, with the mu and kappa opiate agonists having significantly greater effects at night. There were also prominent sex differences in responses; male deer mice displaying significantly greater levels of mu and kappa opiate-induced analgesia and alterations in activity than female animals. These sex differences in opiate-induced effects were most pronounced at night, female deer mice displaying reduced day-night rhythms of responsiveness. These results demonstrate the existence of significant day-night rhythms and sex differences in the mu and kappa opiate behavioral responses of a wild population of rodents.

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

Aggression, defeat and opioid activation in mice: influences of social factors, size and territory.

The aggressive components and opioid-mediated behavioral consequences of various types of intraspecific agonistic interactions between individual male mice were examined. The size of the animals, their previous social history (group or isolation housing) and territory on which the encounter took place were varied to yield 26 different 'resident-intruder' paradigms. In these agonistic encounters the latency to first attack, number of bites and time to defeat, as well as the number of attack bouts present varied according to the 'resident-intruder' paradigm employed. The behavioral consequences of aggression and defeat, including analgesia, increased activity and augmented feeding were determined from the subordinate mice in 5 representative agonistic interactions. These behavioral responses, which had been previously shown to be mediated by endogenous opioid systems also varied according to the 'resident-intruder' paradigm employed. When both mice were group-housed, there was no agonistic behavior, regardless of the size of the mice or the testing arena. In isolated animals the defeat posture was only observed in 1 of the 19 paradigms. It is suggested that various 'resident-intruder' pairings and agonistic interactions can provide a reliable and useful means of examining differential naturalistic stress-induced endogenous opioid activation.

Aggression↗

Magnetic fields and stress: day-night differences.

An exposure for 30 min to a 0.5 Hz rotating magnetic field (1.5-90 G) significantly reduced warm water swim stress-induced opioid analgesia in CF-1 male mice. Pre-treatment with naloxone (1.0 mg/kg) had comparable inhibitory effects on warm water swim induced analgesia. The magnetic stimuli also eliminated the day-night rhythm in stress-induced analgesia, with maximum inhibitory effects occurring in the dark period when peak analgesia was present. These results indicate that magnetic stimuli can significantly alter day-night rhythms of stress-induced activation of endogenous opioid systems and their behavioral and physiological consequences. These elevated night time effects may involve actions on the pineal gland, while the day time actions may involve alterations in the distribution and transport of Ca++ and or other divalent ions.

Animals↗

Attenuation of morphine-induced analgesia in mice by exposure to magnetic resonance imaging: separate effects of the static, radiofrequency and time-varying magnetic fields.

Exposure of adult male mice to a magnetic resonance imaging (MRI) procedure has been shown to abolish the nocturnal analgesic responses observed following treatment with morphine. The field component(s) responsible for this inhibitory effect were examined by exposing mice to either the static, time-varying or rf magnetic field components associated with an MRI procedure. In the middle of the night portion of their day-night cycle, mice were exposed for 23.2 min to one of the above field components, intraperitoneally injected with morphine sulphate (10 mg/kg) and then exposed to the field conditions for another 23.2 min, after which analgesic responses were determined. Analgesia was quantitated by determining the length of time mice were content to be on a hot surface (50 degrees C) before they showed discomfort by licking their paws. It was observed that the time-varying magnetic field completely abolished, the rf field significantly reduced, while the static field component (0.15 T) had no evident effect on morphine-induced analgesia. These results indicate that the time-varying, and to a lesser extent the rf, fields associated with the MRI procedure inhibit morphine-induced analgesia in mice. These data also raise the possibility that exposure in humans to some of the magnetic field components associated with MRI may have clinically relevant effects on the actions of narcotic drugs such as morphine.

Animals↗

Slugs and snails and opiate tales: opioids and feeding behavior in invertebrates.

There is accumulating evidence that opioid systems are involved in the regulation of fundamental behavioral and physiological processes in invertebrates. Feeding is a basic physiological function that is essential for maintaining homeostasis. Results of studies examining the feeding responses of molluscs and arthropods treated with various opiate agonists and antagonists indicate that delta, kappa, mu, and possibly sigma opioid systems differentially and selectively mediate the components of their natural feeding behavior. Moreover, it appears that at an early evolutionary stage the mu and kappa systems have developed to selectively affect the components of feeding behavior associated with the acquisition and ingestion of food. In addition, evidence suggests that neuropeptides that have been proposed as possible endogenous antagonists of opioid-mediated feeding in mammals may also be involved in the control of feeding in invertebrates. This indicates that there may be an interplay of opioid agonists and antagonists in the regulation of feeding and satiation in invertebrates analogous to that proposed for vertebrates. Moreover, these findings indicate that opioid influences on feeding have been conserved through evolution.

Animals↗