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Biomedical subjects

K P Ossenkopp

Publications and source records attributed to K P Ossenkopp.

At least 91 records · Page 5Linked to original sources

Conditioned taste aversions and changes in motor activity in lithium-treated rats. Mediating role of the area postrema.

The role of the area postrema in mediating taste aversions conditioned with the administration of lithium was examined in experiment 1. Rats with lesions of the area postrema or with sham lesions were given pairings of a novel taste with either intraperitoneally or intragastrically administered lithium chloride (LiCl; 10 mg/kg of a 0.15 M solution of lithium chloride) or a similar concentration of NaCl (control groups). Sham-lesioned rats exhibited strong taste aversions when lithium was used for the conditioning procedure and given intraperitoneally or intragastrically (P less than 0.01). Rats with lesions of the area postrema failed to develop taste aversions after the administration of lithium by either route. In experiment 2, rats with lesions of the area postrema and rats with sham lesions were given 30 min access to a 0.12 M solution of NaCl and 2 days later to a 0.12 M solution of lithium. The sham-lesioned animals drank less lithium than NaCl (P less than 0.02) and exhibited depressions in levels of activity following the ingestion of lithium. Rats with lesions of the area postrema drank more lithium than the sham-lesioned rats (P less than 0.01) and did not show behavioral depression after the ingestion of lithium. These data suggest that in the absence of the chemically-sensitive area postrema intragastrically administered lithium does not produce conditioned taste aversions or depression of activity in rats.

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Motor activity changes and conditioned taste aversions induced by administration of scopolamine in rats: role of the area postrema.

Three experiments examined the effects of centrally and peripherally acting scopolamine (scopolamine hydrochloride-SHC) or only peripherally acting scopolamine (scopolamine methyl nitrate-SMN), on motor activity levels and the ability of these agents to induce taste aversions. In Experiment 1 rats were injected with isotonic saline, 1 mg/kg SHC, or 1 mg/kg SMN. SHC produced significant increases in stabilimeter activity (p less than 0.025) and in rearing response frequency (p less than 0.01), whereas SMN resulted in significantly less activity (p less than 0.025). Both agents induced strong conditioned taste aversions to saccharin (p less than 0.01). Experiment 2 examined the role of the area postrema in mediating these drug induced behavioral changes. Sham lesioned and area postrema lesioned rats were given saline, SHC or SMN (1 mg/kg for both drugs) and examined for changes in activity, rearing response frequency and induction of taste aversions to saccharin. SHC again produced significant increases in activity (p less than 0.01), whereas SMN produced decrements in activity (p less than 0.05). However, the brain lesion did not consistently alter the effects of these drugs on activity but it did reduce the amount of the decrement observed in rearing responses in SMN treated rats. The brain lesion also altered the ability of the drugs to induce taste aversions. Both SMN and SHC produced strong taste aversions in the sham lesioned rats (p less than 0.01) but no significant aversions were observed in the area postrema lesioned rats. Experiment 3 examined the ability of the brain lesion to alter the effects of SMN by using a within groups design. Area postrema lesions were found to attenuate but not abolish, the inhibitory effects of SMN on both activity levels and rearing responses (p less than 0.03). The results of these experiments suggest that in the absence of the chemically-sensitive area postrema both SMN and SHC fail to induce taste aversions and the inhibitory effect of SMN on spontaneous activity is attenuated.

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Behavioral effects of exposure to nuclear magnetic resonance imaging: I. Open-field behavior and passive avoidance learning in rats.

The effect of exposure to the magnetic and radio-frequency fields associated with Nuclear Magnetic Resonance Imaging (MRI) on two standard animal behavior tests, was examined in rats. In the first experiment male rats were given a baseline open-field test and 48 hrs later exposed for 22.5 min to a MRI procedure, a sham imaging procedure, or a control condition. Immediately after this exposure period a second open-field test was administered. All animals were given 4 more daily exposures to their respective treatment conditions and after the last exposure period a third open-field test was given. Analysis of open-field ambulation, rearing, and defecation responses indicated no significant effect of exposure to MRI on these behaviours. In a second experiment rats were conditioned in a step-down passive avoidance task and then exposed for 23.2 min (48 hrs later) to MRI, sham imaging, or control conditions. Retention tests for the passive avoidance response were administered after the first and fifth daily exposure to the experimental treatment conditions. No significant effects of the treatment conditions on retention of the avoidance response were obtained and a third retention test 3 months after the second test, also failed to provide any evidence for treatment effects. These results fail to provide any evidence for short or long term behavioral changes in animals exposed to MRI.

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Behavioral effects of exposure to nuclear magnetic resonance imaging: II. Spatial memory tests.

In order to determine possible effects of exposure to nuclear magnetic resonance imaging (MRI) on cognitive processes, the performance of imaged, sham exposed, and control rats on a spatial memory task was examined. This particular task was chosen because, under some conditions, animals use the magnetic field as a compass when navigating. The rats were required to collect food from eight different locations before returning to an already chosen location. All three groups of rats achieved a high level of performance, and there were no differences between groups in any of the performance measures examined. These results indicate that the MRI procedure has no significant effect on spatial memory processes in rats.

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Taste aversions conditioned with multiple exposures to gamma radiation: abolition by area postrema lesions in rats.

Lesions which destroy the area postrema (AP) and damage the adjacent nucleus of the solitary tract (NTS) attenuate conditioned taste aversions (CTA) induced by a variety of pharmacological agents as well as exposure to radiation. In this experiment the possibility that AP lesions might not attenuate a radiation-induced CTA, when multiple pairings of the novel taste stimulus and exposure to gamma radiation occurred, was examined. Three groups of male rats received lesions of AP and another 3 groups received sham lesion. Following a recovery period all rats were adapted to a 23.5 h/day water deprivation schedule. A sodium saccharin solution (0.1%) was offered to all rats during the regular drinking period (0.5 h) on two days per week, with water available on the other days. Access to saccharin was followed by exposure to 0, 20 or 40 rad of gamma radiation with one lesioned and one sham-lesioned group assigned to each dose level. After 4 pairings of saccharin with radiation the sham-lesioned groups exposed to 20 and 40 rad of radiation exhibited a dose-dependent aversion to the saccharin solution (P less than 0.0001), whereas the AP-lesioned groups did not differ significantly from the 0 rad sham-lesioned group. Subsequent two-bottle choice tests, which are a more sensitive measure of CTA, confirmed that the AP-lesioned rats exposed to 20 and 40 rad radiation did not develop a significant CTA relative to the two 0 rad radiation groups. Thus, AP lesions abolished the CTA normally induced by multiple pairings of saccharin with exposure to 20 or 40 rad gamma radiation.

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Exposure to nuclear magnetic resonance imaging procedure attenuates morphine-induced analgesia in mice.

Adult male mice exposed to a Nuclear Magnetic Resonance Imaging (NMRI) procedure during the mid-dark period and injected with morphine (10 mg/kg) failed to exhibit the normal nocturnally enhanced morphine analgesia response to a thermal stimulus that was displayed by mice exposed to a sham imaging procedure and treated with morphine (p less than .01). When tested during the mid-light period, animals exposed to the NMRI procedure and given morphine displayed attenuated analgesia levels relative to sham exposed mice (p less than .01) treated with morphine. However, the morphine induced analgesia was not totally abolished since the imaged mice still exhibited analgesia relative to saline treated mice (p less than .01). These results suggest that the magnetic and/or radio-frequency fields associated with the NMRI procedure alter both day- and night-time responses to morphine. These results may reflect magnetic field induced alterations in neuronal calcium binding and/or alterations in nocturnal pineal gland activity.

Analgesia↗

Tolerance to morphine-induced analgesia in mice: magnetic fields function as environmental specific cues and reduce tolerance development.

Mice receiving daily injection of morphine (10 mg/kg) developed tolerance to morphine-induced analgesia, such that after 5-7 days of treatment their thermal response (paw licking) latencies in the hot plate test were indistinguishable from those of control animals. Exposure to a rotating magnetic field for thirty minutes before the daily morphine administrations significantly reduced the development of tolerance. These magnetic exposures also significantly increased over 7-10 days the basal nociceptive thresholds and paw licking response latencies of saline treated mice. Control and sham exposed mice that were fully tolerant to the analgesic effects of morphine failed to show any tolerance to morphine-induced analgesia when exposed to the magnetic stimuli prior to injection. Likewise, the partial tolerance to morphine shown by mice exposed to the rotating magnetic field pre-injection environmental cues was eliminated when control or sham pre-injection cues lacking the magnetic stimuli were provided. In all cases tolerance to morphine-induced analgesia was evident in the subsequent re-test with the original cues. These results indicate that magnetic field exposure can reduce the development of tolerance to the analgesic effects of morphine. They also show that magnetic stimuli function as significant environmental cues for the development of tolerance to morphine-induced analgesia. This suggests that magnetic stimuli affect both the associative (classical conditioning) and non-associative (physiological, pharmacological) mechanisms involved in the development of opiate tolerance.

Analgesia↗

Exposure to rotating magnetic fields alters morphine-induced behavioral responses in two strains of mice.

An exposure for 60 min to a 0.5 Hz rotating magnetic field (1.5-90 G) significantly reduced the day-time analgesic and locomotory effects of morphine (10 mg/kg) in CF-1 and C-57BL strains of mice, respectively. Exposure to lower intensity 60 Hz magnetic fields (0.-1.0 G) had no effect on analgesia induced by morphine. The reduction in responsiveness to morphine after exposure to the greater intensity rotating field was not evident 24 hr later. No changes were seen in the latencies of basal thermal responses or levels of activity of saline-treated mice exposed to the magnetic stimuli.

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Some behavioral factors related to the effects of cold-restraint stress in rats: a factor analytic-multiple regression approach.

Recently, some individual differences in rats have been shown to be related to stress-induced physiological responses. As yet there has been no attempt to incorporate measurement techniques from the psychometric field to this line of research. The present study was conducted to examine the utility of applying such methods to animal research. Physiological responses to cold-restraint stress in 26 male rats were investigated using a factor analytic-multiple regression procedure. Nineteen behavioral and physiological measures obtained during open-field testing, motor activity monitoring, and passive avoidance learning were subjected to a principle components factor analysis. Five factors were extracted which reflected exploratory behavior, general activity level, metabolic rate, behavioral reactivity, and autonomic reactivity. The obtained factor scores were used to predict physiological responses to four hours of supine cold-restraint using a step-wise multiple regression procedure. General activity level was the best predictor of adrenal weight and temperature loss. Autonomic reactivity was the best predictor of ulcer incidence and severity. Applications of these statistical procedures are discussed.

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Magnetic fields inhibit opioid-induced feeding in the slug, Limax maximus.

Exposure to rotating and elevated magnetic fields significantly reduced over three hours the ingestive effects of the opiate agonist, morphine (10 mg/kg), in free-feeding slugs, Limax maximus. Magnetic field exposure also inhibited the opioid-mediated increased ingestive responses of slugs that had been food-deprived for 24 hr. These results suggest that magnetic stimuli inhibit opiate-mediated behavioral and physiological functions in invertebrates in a similar manner as observed in vertebrates.

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Magnetic fields as environmental specific cues for morphine-induced analgesia: interactions with tolerance development.

It has been previously demonstrated that weak fluctuating magnetic fields can act as environmental specific cues for the development of tolerance to morphine-induced analgesia in mice. During the course of this tolerance development the basal nociceptive response of the animals preexposed to magnetic fields are also increased. The magnetic field-induced increase in the basal nociceptive response can be blocked by the opiate antagonist, naloxone, suggesting an opioid-mediated stress effect of the magnetic stimuli. It is suggested that part of the actions of the magnetic stimuli as environmental specific stimuli may arise through their actions as stressors during the tolerance acquisition phase, as well as from their effects on opioid systems.

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Conditioned taste aversions induced by 1-5-hydroxytryptophan are mediated by the area postrema.

Previous studies have shown that injections of 5-HTP can induce conditioned taste aversions when paired with a novel taste. Adult male albino rats received either lesions of the area postrema or were subjected to a sham lesion procedure. All rats were adjusted to a 23 1/2 hr/day water deprivation schedule and on the conditioning day were given a 0.15% saccharin solution for 1/2 hr. After drinking the saccharin fluid 9 area postrema lesioned and 10 sham lesioned rats were injected i.p. with 25 mg/kg 1-5-hydroxytryptophan. Similarly 10 area postrema lesioned and 6 sham lesioned rats were injected with the vehicle solution. A two-bottle choice test between the saccharin solution and water was given to all animals on the third and fourth days after the conditioning day. The sham lesioned rats injected with the 1-5-hydroxytryptophan exhibited a strong aversion to the saccharin taste whereas the vehicle injected sham lesioned rats showed an equal preference for the two fluids. The difference in group mean saccharin preference ratio was significant (p less than .01). Both area postrema lesioned groups exhibited saccharin preference ratios that were comparable to and not significantly different from the sham lesioned animals injected with the vehicle solution. These results show that an intact area postrema is necessary for induction of conditioned taste aversions with 1-5-hydroxytryptophan.

5-Hydroxytryptophan↗

Magnetic fields abolish the enhanced nocturnal analgesic response to morphine in mice.

Mice given morphine displayed diel rhythms in the latency of their behavioral response to placement on a hot plate, there being a several fold increase in their nocturnal reaction times. Exposure to a rotating magnetic field eliminated the day-night analgesia rhythms, reducing over 5-10 days the enhanced nocturnal latencies to those found during the day. The attenuation returned to normal nocturnal levels several days after removal of the rotating magnetic field and could be subsequently re-established by reapplication of the magnetic field condition. It is suggested that these changes in analgesia may reflect alterations in the activity of the pineal gland during exposure to magnetic fields.

Analgesia↗

Motion sickness in quail: body-rotation-induced conditioned fluid aversions in C. coturnix japonica.

The presence of motion sickness in Japanese quail (C. coturnix japonica) was examined by using a conditioned fluid aversion as an index. Twenty-three birds were divided into three groups. One group received a novel fluid (yellow-sour water) followed by 30 min of body rotation at 70 rpm (on a schedule of 15 s on and 5 s off). Another group received the novel fluid followed by exposure to a sham rotation procedure. The third group experienced the rotation procedure following access to water. The group receiving the rotation procedure contingent on presentation of the novel fluid exhibited a conditioned aversion to this fluid (relative to the control groups) over days of acquisition (p less than .025) which subsequently dissipated when rotation was no longer contingent on the presentation of the yellow-sour water (extinction). These data thus demonstrate the presence of motion sickness in a gallinaceous species as indexed by a conditioned fluid aversion procedure.

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Reduced nocturnal morphine analgesia in mice following a geomagnetic disturbance.

Latency to respond to an aversive thermal stimulus and the degree of analgesia induced by morphine were examined in mice injected with either isotonic saline or morphine sulfate (10 mg/kg) during midscotophase of a 12:12 h LD cycle. When mean response latencies were compared to the degree of geomagnetic disturbance (Ap index) present on test days, it was found that during the geomagnetic storm on December 17th, 1982, a significant reduction (P less than 0.01) in response latency was evident in both saline- and morphine-treated mice. The reduction in response latencies was greater, and lasted longer in the morphine-treated animals. It is suggested that the pineal gland may mediate this biomagnetic effect.

Analgesia↗

Taste aversions conditioned with gamma radiation: attenuation by area postrema lesions in rats.

The role of the area postrema in radiation induced taste aversions in rats was examined. One group of rats received lesions of the area postrema, another group was given sham lesions and a third group received no surgery. These three groups of rats were then given one pairing of 1 h access to a novel 0.15% sodium saccharin solution followed immediately with exposure to 200 rad gamma radiation. A fourth group of rats with area postrema lesions was given 1 h access to saccharin followed by a sham irradiation procedure. Four days later all groups were given daily two bottle preference tests (saccharin vs water) on 5 consecutive days. The groups with sham lesions or no surgery displayed a strong aversion to saccharin on all 5 test days. The two area postrema lesioned groups displayed a moderate and increasing preference for saccharin over the 5 day test period. The lesioned group given radiation treatment showed a weak but significant aversion (P less than 0.05) to saccharin on the first test day, when compared to the lesioned rats not given radiation treatment. Thus, lesions of the area postrema strongly attenuated the radiation induced taste aversions, but did not completely abolish them.

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Area postrema lesions in rats enhance the magnitude of body rotation-induced conditioned taste aversions.

The role of the area postrema, a circumventricular organ located on the dorsal medulla in the fourth ventricle, in body rotation-induced conditioned taste aversions was examined in male hooded rats. One group of rats received lesions of the area postrema, another group was given sham lesions, and two other groups received no surgery. Three groups of rats, those with area postrema lesions, those with sham lesions, and one unoperated group, were given pairings of 1-hr access to a 0.1% sodium saccharin solution with 30 min of body rotation at 70 rpm (on a schedule of 15-sec on--5-sec off). A fourth group of unoperated rats was given pairings of access to the saccharin solution with 30 min of sham rotation. The three rotated groups all developed a taste aversion to the saccharin solution whereas the sham-rotated group did not. The group with lesions of the area postrema exhibited a greater aversion to the saccharin taste than the other two rotated groups. In a second phase of the experiment all rats were given pairing of 1-hr access to chocolate milk with injections of scopolamine methyl nitrate (1 mg/kg). The area postrema-lesioned group failed to exhibit a taste aversion to the chocolate milk whereas the other groups all showed very strong aversions. It was concluded that area postrema lesions abolish taste aversions induced by blood-borne toxins such as scopolamine methyl nitrate, but enhance taste aversions induced by motion sickness. Some speculations concerning the enhanced taste aversions induced by motion sickness in area postrema lesioned rats, are provided.

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