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Biomedical subjects

K P Ossenkopp

Publications and source records attributed to K P Ossenkopp.

At least 73 records · Page 4Linked to original sources

Motion sickness in guinea pigs (Cavia porcellus) indexed by body rotation-induced conditioned taste aversions.

The presence of motion sickness in albino guinea pigs (Cavia porcellus) was examined by using a conditioned taste aversion (CTA) as an index. Eighteen animals were divided into three groups. One group received four pairings of a novel 0.15% saccharin solution followed by 20 min of body rotation at 70 rpm (on a schedule of 15 sec on and 5 sec off). Another group received four pairings of the saccharin solution followed by exposure to sham rotation. The third group experienced the rotation procedure following access to water. The group receiving the rotation procedure contingent on presentation of the novel saccharin taste exhibited a conditioned aversion to this fluid (relative to the control groups) over days of acquisition (p less than 0.01), which subsequently dissipated when rotation was no longer contingent on the presentation of the saccharin solution (extinction). These data thus demonstrate the presence of motion sickness in guinea pigs when CTA is used as an index.

Animals↗

Sodium arsanilate-induced vestibular dysfunction in rats: effects on open-field behavior and spontaneous activity in the automated digiscan monitoring system.

Vestibular dysfunction was chemically induced in Long-Evans rats by intratympanic injections (30 mg per side) of sodium arsanilate (atoxyl). Following a one-week recovery period the rats were behaviorally assayed for integrity of the labyrinthine systems. All subjects were tested for presence of the air-righting reflex, the contact-righting reflex (by lightly holding a sheet of Plexiglas against the soles of the rat's feet), and body rotation-induced nystagmus. All animals were then tested for their ability to remain on a small (15 x 15 cm) platform. Next, the subjects were given two 10-min open-field tests during which ambulation, rearing, grooming, and defecation responses were recorded. Four to five weeks later all rats were tested twice (60 min per session) in the automated Digiscan Activity Monitor which provides a multivariate assessment of spontaneous motor activity. The rats with vestibular dysfunction (Group VNX) took significantly less time to fall off the platform (p less than 0.01). They also exhibited significantly more open-field ambulation but fewer rearing responses (ps less than 0.01). An examination of group correlation coefficients for open-field variables and the platform test scores revealed some interesting group differences (ps less than 0.05). In the Digiscan tests the atoxyl-treated rats exhibited fewer number of horizontal movements, but increased speed for these movements (ps less than 0.05). Vertical movements did not differ significantly in incidence, but these movements were greatly reduced in duration (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Nicotine-induced conditioned taste aversions are enhanced in rats with lesions of the area postrema.

Lesions, which destroy the area postrema and damage the adjacent nucleus of the solitary tract, attenuate or abolish conditioned taste aversions (CTA) induced by a variety of pharmacological agents. In the present experiment 2 groups of male rats received lesions of the area postrema and 2 groups were given sham lesions. One lesioned group and one sham-lesioned group were twice conditioned with 30-min access to a novel 0.15% saccharin solution followed by injection of nicotine (1 mg/kg, IP). The other 2 groups were similarly conditioned with saccharin followed by saline injections. In subsequent two-bottle choice tests (saccharin vs. water), the saline-injected rats exhibited strong preferences for saccharin, the sham-lesioned rats injected with nicotine showed a weak but significant (p less than 0.05) aversion to saccharin, and the area postrema-lesioned rats injected with nicotine displayed a significantly (p less than 0.05) stronger CTA than the drug-injected sham-lesioned animals. In Phase 2 all rats were given novel chocolate metrecal (30 min) followed by injection of scopolamine HCl (1 mg/kg, IP). The area postrema-lesioned rats showed significant (p less than 0.01) preference for the chocolate taste relative to the aversions shown by the sham-lesioned animals. Thus, area postrema lesions attenuated a scopolamine-induced CTA, but enhanced a nicotine-induced aversion. These results suggest that nicotine and scopolamine act at different neural sites in producing CTAs.

Animals↗

Absence of a hemispheric difference in seizure sensitivity and kindling rate in the rat brain.

The question of a population hemispheric asymmetery in initial seizure sensitivity and in rate of kindling in the amygdala was examined in an unbiased sample of 80 rats studied in our laboratory during the past six years. Afterdischarge threshold, initial and final afterdischarge duration, and kindling rate were the same in rats kindled in the left or right basolateral amygdala. The results suggest that there is no systematic difference between the hemispheres in initial seizure sensitivity or rate of amygdala kindling.

Amygdala↗

Gamma radiation-induced conditioned taste aversions in rats: a comparison of the protective effects of area postrema lesions with differing doses of radiation.

Lesions which destroy the area postrema (AP) and damage the adjacent nucleus of the solitary tract (NTS) attenuate or abolish conditioned taste aversions (CTA) induced by a variety of pharmacological agents as well as exposure to radiation. In the present experiment, 4 groups of male rats received lesions of AP and 4 groups were given sham lesions. One sham-lesioned and one AP-lesioned group were given a single pairing of 1-hr access to a novel 0.10% sodium saccharin solution followed immediately with exposure to 0, 100, 200, or 400 rad of gamma radiation, respectively. Four days later all groups were given daily two-bottle preference tests (saccharin vs. water) on 4 consecutive days. The sham-lesioned groups exposed to the radiation (100, 200, or 400 rad) developed profound aversions to the saccharin on all test days (p less than 0.001). In contrast, all of the AP-lesioned groups as well as the sham-irradiated (0 rad) sham-lesioned group exhibited strong, comparable (p greater than 0.30) preferences for saccharin. Thus, lesion of AP abolished the radiation-induced CTA at all dose levels of radiation. These results raise the possibility of pharmacological intervention at the level of AP to prevent radiation-induced CTA in cancer patients undergoing radiation therapy.

Animals↗

The effects of naloxone on body rotation-induced analgesia and anorexia in male mice.

The effects of body rotation in a horizontal plane and the opiate antagonist, naloxone, on the nociceptive responses and the feeding behavior of male mice were examined. In the first experiment the mice were rotated (70 rpm, schedule of 15 sec on; 5 sec off) for 60 minutes or exposed to sham rotation for the same duration. Midway through the rotation or sham procedure the mice were either injected with naloxone (1 mg/kg) or isotonic saline. At the end of the 60-minute treatment period the animals were placed on a warm surface (47.5 degrees C) and their latency to show a foot-licking response was measured. The rotation procedure produced a significant (p less than 0.01) increase in response latency in the saline-injected mice and the naloxone injections blocked this analgesic effect. This finding provides evidence for opioid involvement in the rotation-induced analgesia. In Experiment 2 mice on a food restriction schedule were rotated (70 rpm, 15 sec on; 5 sec off) or sham exposed for 60 minutes. Midway through this treatment period the mice were either injected with naloxone (1 mg/kg) or isotonic saline. Following the treatment period the mice were given access to food for 2 hours. The rotation procedure produced a significant (p less than 0.01) reduction in feeding (anorexia) in the first 30 minutes of food access for the saline-injected mice. Injections of naloxone significantly (p less than 0.05) enhanced the rotation-induced anorexia. These experiments demonstrate that rotation-induced analgesia in mice is blocked by the opiate antagonist, naloxone, whereas rotation-induced anorexia is not.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗

Inhibitory effects of acute exposure to low-intensity 60-Hz magnetic fields on electrically kindled seizures in rats.

The possibility that exposure to power-line frequency (60-Hz) magnetic fields might affect the development or characteristics of epileptic seizures in electrically kindled rats, was examined. Male adult rats with electrodes implanted in the basolateral amygdala were exposed to either a 60-Hz, 1.0 gauss magnetic field or to a sham field condition for 1 h prior to each daily brain stimulation session. EEG recordings were made to measure afterdischarge characteristics after each daily brain stimulation. Once the animals exhibited a full stage 5 seizure (after approximately 12-15 stimulations) a cross-over manipulation was used. On the last test day the sham field control group was exposed to the 60-Hz magnetic field for 1 h prior to brain stimulation and the experimental group, normally exposed to the magnetic fields, was exposed to the sham field condition. Examination of afterdischarge durations revealed a weak retardation in the development of kindling in the experimental group (P = 0.08). In the cross-over test, exposure to the 60-Hz magnetic fields resulted in a significant (P = 0.019) inhibition in afterdischarge duration relative to the rats exposed to the sham field conditions. These results clearly suggest an inhibitory effect of acute exposure to low intensity 60-Hz magnetic fields on the duration of afterdischarges in electrically kindled rats. Possible mechanisms for such an effect are discussed.

Animals↗

Exposure to time varying magnetic fields associated with magnetic resonance imaging reduces fentanyl-induced analgesia in mice.

The effects of exposure to clinical magnetic resonance imaging (MRI) on analgesia induced by the mu opiate agonist, fentanyl, was examined in mice. During the dark period, adult male mice were exposed for 23.2 min to the time-varying (0.6 T/sec) magnetic field (TVMF) component of the MRI procedure. Following this exposure, the analgesic potency of fentanyl citrate (0.1 mg/kg) was determined at 5, 10, 15, and 30 min post-injection, using a thermal test stimulus (hot-plate 50 degrees C). Exposure to the magnetic-field gradients attenuated the fentanyl-induced analgesia in a manner comparable to that previously observed with morphine. These results indicate that the time-varying magnetic fields associated with MRI have significant inhibitory effects on the analgesic effects of specific mu-opiate-directed ligands.

Analgesia↗

Magnetic fields inhibit opioid-mediated 'analgesic' behaviours of the terrestrial snail, Cepaea nemoralis.

1. The terrestrial snail, Cepaea nemoralis, when placed on a warmed surface (40 degrees C) displays a thermal avoidance behaviour that entails an elevation of the anterior portion of the fully extended foot. The latency of this nociceptive response was increased by the prototypical mu and specific kappa opiate agonists, morphine and U-50, 488H, respectively, in a manner indicative of anti-nociception and the induction of 'analgesia'. Pretreatment with the prototypical opiate antagonist, naloxone, blocked the morphine- and reduced the U-50, 488H-induced analgesia. Naloxone had no effects on the thermal response latencies of saline treated animals. 2. Exposure to either cold (7 degrees C) or warm (38 degrees C) temperature stress increased the nociceptive thresholds of Cepaea in a manner indicative of the induction of 'stress-induced analgesia'. The warm stress-induced analgesia was opioid mediated, being blocked by naloxone, whereas, the cold stress-induced analgesia was insensitive to naloxone. 3. Exposure for 15-30 min to 0.5 Hz weak rotating magnetic fields (1.5-8.0 G) significantly reduced the analgesic effects of the mu and kappa opiate agonists in a manner similar to that observed with naloxone. The magnetic stimuli also inhibited the endogenous opioid mediated warm stress-induced analgesia and significantly reduced the cold stress-induced analgesia. The magnetic stimuli had no evident effects on the nociceptive responses of saline-treated animals. The dihydropyridine (DHP) and non-DHP calcium channel antagonists diltiazem, verapamil. and nifedipine differentially and significantly reduced, while the DHP calcium channel agonist, BAY K8644, significantly enhanced the inhibitory effects of the magnetic fields on morphine-induced analgesia.

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

Body-rotation induced analgesia in male mice: effects of duration and type of rotation procedure.

The effects of body-rotation in a horizontal plane on the nociceptive responses of male mice were examined. In the first experiment the mice were rotated (70 rpm, schedule of 15 sec on; 5 sec off) for 30 minutes or exposed to sham rotation. The animals were then placed on a warm surface (47.5 degrees C) and their latency to show a foot-licking response was measured. Immediately after the preceding rotation procedure a trend toward a significant increase in response latencies, indicative of analgesia, was observed (p = 0.057). However, if tested 30 minutes after the end of the rotation period, no analgesia could be demonstrated (p greater than 0.50). In Experiment 2 mice were rotated (15 sec on; 5 sec off) or sham rotated for durations of 60 or 90 minutes. Response latencies were significantly elevated (p less than 0.01) after both rotation durations, but not differentially so (p greater than 0.20). In the last experiment the effects of 60 minutes of the intermittent rotation procedure (15 sec on; 5 sec off) were compared to those of 60 minutes of continuous rotation. Both types of rotation resulted in the induction of analgesia and the intermittent procedure produced a significantly greater degree of analgesia than the continuous rotation (p less than 0.05). These experiments demonstrate that 60 to 90 minutes of body-rotation can produce a significant "stress-induced" analgesia in mice and that an intermittent schedule of rotation is more effective than a continuous rotation exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗

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 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↗

Automated multivariate measurement of spontaneous motor activity in mice: time course and reliabilities of the behavioral measures.

A variety of automated procedures have been developed to measure certain aspects of spontaneous motor activity in small animals. The present study used a Digiscan Animal Activity Monitor to measure six different aspects of spontaneous motor behavior in male CF-1 mice. The Digiscan system uses infrared beams and computer analysis to quantify various behavioral variables. The mice were tested for 1 hour on 2 different days of the week for 3 consecutive weeks. Both the temporal changes in the measured variables and the test-retest reliabilities were examined in a group of 30 mice. Statistical analysis of the data revealed significantly higher mean values for total movement time, average distance travelled, and horizontal activity on the first test session relative to the second session (p less than 0.01). The other 3 measures, total distance travelled, number of movements, and average speed, did not vary significantly across test sessions. All 6 behavioral variables showed good test-retest reliabilities and these could be increased by aggregating the data on a weekly basis. The present results indicate that the measures obtained from the Digiscan system are reliable and that the animals should first be habituated to the test apparatus in order to obtain stable baseline activity values.

Animals↗

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↗

Survivability and long-term stress reactivity levels following repeated exposure to nuclear magnetic resonance imaging procedures in rats.

The effect of exposure to the magnetic and radio-frequency fields associated with Nuclear Magnetic Resonance Imaging (MRI) on survivability and long-term stress reactivity levels was examined in male rats. Rats in the experimental condition were exposed to MRI for 22.5 minutes for five successive days (Expt. 1) or 23.3 minutes for twenty-one successive days (Expt. 2). Sham field exposed animals received the identical treatment as the exposed animals except that the magnetic and radio-frequency fields were absent. Control rats were also maintained. Thirteen to twenty-two months after the exposure procedure the remaining rats were sacrificed and their whole body, spleen, heart, thymus, and adrenal weights were recorded. Blood samples were taken for measurements of red and white blood cell counts, hemoglobin content, as well as adrenocorticotrophin and corticosterone levels. The results fail to provide any evidence for changes in survivability and long-term stress reactivity levels in rats exposed to MRI and thus give no grounds to challenge the view that MRI is a safe diagnostic procedure.

Adrenocorticotropic Hormone↗

Magnetic field inhibition of morphine-induced analgesia and behavioral activity in mice: evidence for involvement of calcium ions.

An exposure for 60 min to a 0.5 Hz rotating magnetic field (1.5-90 G) significantly reduced the day-time analgesic (in CF-1 mice) and locomotory (in C-57BL mice) effects of morphine (10 mg/kg). Intracerebroventricular (i.c.v.) injections of a calcium chelator, EGTA, blocked these effects, while administration of the calcium ionophore, A23187, potentiated the inhibitory actions. In a parallel fashion, i.c.v. administration of Ca2+ reduced, in a dose-related manner, the analgesic and locomotory effects of morphine in control CF-1 and C57 mice. These latter inhibitory effects could also be blocked by EGTA and augmented by A23187, indicating that opiate effects on activity and nociception are both sensitive to antagonism by calcium. Taken together these results suggest that exposure to magnetic stimuli may alter morphine-induced responses in mice, in a manner compatible and consistent with effects on Ca2+ and possibly other divalent ions.

Analgesia↗

Stress-induced opioid analgesia and activity in mice: inhibitory influences of exposure to magnetic fields.

An exposure for 30 min to a 0.5 Hz rotating magnetic field (1.5-90 G) significantly reduced immobilization stress-induced, opioid analgesia and hyperactivity in CF-1 and C-57 BL strains of mice, respectively. The magnetic exposure also eliminated the day-night rhythm in stress-induced analgesia, with maximum inhibitory effects occurring in the dark period. Pre-treatment with naloxone (1.0 mg/kg) had comparable inhibitory effects on immobilization-induced analgesia and activity. These results suggest that exposure to magnetic stimuli can significantly influence stress-induced activation of endogenous opioid systems and their behavioral and physiological consequences.

Animals↗