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Biomedical subjects

K P Ossenkopp

Publications and source records attributed to K P Ossenkopp.

At least 37 records · Page 2Linked to original sources

Hormone replacement modifies cholecystokinin-induced changes in sucrose palatability in ovariectomized rats.

The taste reactivity test was used to examine the effect of CCK-octapeptide (CCK-8) on the palatability of a sucrose solution in ovariectomized rats either receiving hormonal replacement (estradiol and progesterone; OVX + HRT), or treated with vehicle only (OVX + VEH). Statistical analyses revealed that the OVX + HRT rats treated with CCK-8 exhibited a robust decrease in ingestive responses, and an increase in aversive responses and passive drips to the intraoral sucrose infusions, relative to treatment with the NaCl vehicle. In contrast, a weak effect of CCK-8 on ingestive responses, no significant effect on the frequency of aversive responses, and a reduced effect on passive drips was observed in the OVX + VEH rats. These results show that CCK-8 modifies sucrose palatability, and that this effect is modulated by gonadal hormone levels.

Animals↗

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↗

Taste reactivity responses in rats: influence of sex and the estrous cycle.

Gonadal hormones (e.g., estradiol) may regulate feeding by producing a shift in the taste or palatability of food items. This study examined the impact of endogenous gonadal hormones on palatability by investigating sex differences in taste responsivity, as well as the effect of the estrous cycle on taste responsivity, in a rodent model. In the taste reactivity test, male and female Long-Evans rats received a brief (1 min) intraoral infusion of one of three tastants: sucrose (0.3 M), quinine (0.0003 M), and a sucrose-quinine mixture (0.3 M sucrose and 0.0003 M quinine). Statistical analyses indicated that female rats tested during diestrus or proestrus produced significantly more ingestive responses than did male rats and fewer aversive responses than did both male rats and female rats tested during estrus or metestrus (P < 0.05). These results indicate a sex difference in taste responsivity in the rat that is modulated by the reproductive status of female rats. This finding implies a role of gonadal hormones in the regulation of taste responsivity in the rat.

Animals↗

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↗

Forced-choice discrimination of equimolar NaCl and LiCl solutions in rats: effects of ablating the chemosensitive area postrema on acquisition and retention.

The area postrema (AP), a chemosensitive organ located in the fourth ventricle, has been shown to mediate the formation of a lithium-induced conditioned taste avoidance (CTA) in rats. The present experiments examined the role of the AP in the discrimination between two equimolar solutions of sodium chloride (NaCl) and lithium chloride (LiCl). In the first experiment adult male rats were trained to discriminate between equimolar (0.12 M) solutions of NaCl and LiCl in a forced-choice procedure over a 10-day acquisition phase. Subsequently half of the rats (n = 7) received AP lesions (APX) and the other half (n = 7) were given sham lesions (SHAM). In the retention phase all animals were again exposed to the same salt solutions over a 10-day period. Good discrimination (P < 0.001) between the two salt solutions was demonstrated by the end of the acquisition phase and both the APX and SHAM groups exhibited robust retention (P < 0.01) of this discrimination in the second phase. However, when only a LiCl solution was available the APX group ingested significantly more (P < 0.01) than the SHAM rats. No significant group difference emerged when only NaCl was available. In the second experiment rats received ablations of AP or sham lesions and were then trained to discriminate between 0.12 M NaCl and LiCl solutions in a forced-choice procedure over a 10-day period. Both groups exhibited a clear discrimination (P < 0.01) between the two solutions by the end of the acquisition phase. APX rats ingested significantly more LiCl (P < 0.01) than did the SHAM group when this was the only type of fluid available. Again, no such difference was evident when only NaCl was available. These experiments demonstrate that the AP is not necessary for either the acquisition or retention of a discrimination between equimolar solutions of NaCl and LiCl in a forced-choice procedure and that this discrimination is not mediated by a conditioned taste aversion to the LiCl solution.

Animals↗

Pulsed magnetic field induced "analgesia" in the land snail, Cepaea nemoralis, and the effects of mu, delta, and kappa opioid receptor agonists/antagonists.

A brief exposure to a pulsed magnetic field (Cnp: patent pending) had significant antinociceptive or "analgesic" effects in the land snail, Cepaea nemoralis, as evidenced by an increase in the latency of response to a warmed (40 degrees C) surface. This analgesia was in part opioid mediated being significantly reduced, but not eliminated: by the prototypic opiate antagonist, naloxone; the mu (mu) opioid receptor directed antagonists, naloxazine or beta-funaltrexamine, and the delta (delta) opioid receptor directed antagonists, naltrindole-5'-isothiocyanate or ICI 174,864. However the Cnp induced analgesia was unaffected by the kappa (kappa) opioid receptor directed antagonist, nor-binaltorphimine. The delta 1 and delta 2 opioid receptor directed agonists, (DPDPE, [D-Pen2,D-Pen5]enkephalin), (deltorphin, [D-Ala2,Glu4]), respectively, also had significant differential analgesic effects, supporting a functional delta opioid receptor mediated enkephalinergic mechanism in Cepaea. These results suggest that this specific pulsed magnetic field (Cnp) elicits significant analgesic effects through mechanisms that, in part, involve delta and, to a lesser extent mu opioid receptors.

Analgesia↗

Oestradiol-induced taste avoidance is the result of a conditioned palatability shift.

Taste avoidances were conditioned in male rats by pairing ingestion of a novel sucrose (0.3 M solution) taste with injections of 17 beta oestradiol (100 micrograms kg-1, s.c.). Following conditioning and prior to a two-bottle choice test (sucrose vs water), taste reactivity responses to three 30 s intraoral sucrose infusions were quantified. A robust conditioned shift in palatability, consisting of reduced ingestive and increased aversive taste reactivity responses, was obtained in the oestradiol group but not the vehicle control group. This conditioned palatability shift was also reflected in subsequent strong avoidance of the sucrose solution in the two-bottle choice test. The findings that oestradiol can condition taste aversions and shift food preferences support a role for oestrogens in the production of anorexia.

Animals↗

Spatial learning in deer mice: sex differences and the effects of endogenous opioids and 60 Hz magnetic fields.

We examined the effects of brief exposure to weak 60 Hz extremely low frequency (ELF) magnetic fields and opioid systems on spatial behavior and learning in reproductive adult male and female deer mice, Peromyscus maniculatus. Sex differences were evident in spatial performance, with male deer mice displaying significantly better performance than female mice in the Morris water maze, whereby animals had to acquire and retain the location of a submerged hidden platform. Brief (maximum 5 min) exposure to weak (100 microT) 60 Hz magnetic fields during task acquisition significantly improved female performance, eliminating the sex differences in acquisition. The opiate antagonist, naltrexone, also improved female acquisition, though significantly less than the magnetic fields. These facilitatory effects involved alterations of "non-spatial" (task familiarization and reduction of related anxiety/aversive related behaviors) and possibly "spatial" aspects of the task. Enhancement of enkephalin activity with the enkephalinase inhibitor, SCH 34826, significantly reduced task performance by male deer mice. Both naltrexone and the 60 Hz magnetic fields attenuated the enkephalin mediated reductions of spatial performance. These findings indicate that brief exposure to 60 Hz magnetic fields can enhance water maze task acquisition by deer mice and suggest that these facilitatory effects on spatial performance involve alterations in opioid activity.

Analgesics↗

Sexually dimorphic aspects of spontaneous activity in meadow voles (Microtus pennsylvanicus): effects of exposure to fox odor.

In this study, a multivariate analysis of the locomotor activity of adult, breeding male and female meadow voles (Microtus pennsylvanicus) was conducted. Overall, male voles made more movements and spent more time in the center of the activity chambers than did female voles. The authors further investigated the effects of brief exposure (3 min) to predator (red fox [Vulpes vulpes]) odor and various control odors (butyric acid, extract of orange) on subsequent activity. Control odors had no effects. Immediately following exposure to the fox odor, male voles exhibited significantly lower levels of activity and decreased center time. No significant changes in any activity variable were observed in the female voles following exposure to fox odor. This study provides evidence for sex differences in both basal activity levels of meadow voles and activity following exposure to a predator odor.

Animals↗

Sex differences in performance in the Morris water maze and the effects of initial nonstationary hidden platform training.

Sex differences in rats' performance on a stationary hidden-platform task (spatial task) in the Morris water maze and the effects of initial nonstationary hidden platform training (NSP training) were examined. The NSP training was designed to familiarize rats with the general requirements of the water-maze task without providing spatial information. NSP training led to faster acquisition and improved retention of the subsequent spatial task in both males and females. There was a sex difference favoring males on acquisition and retention of the spatial task only in rats that had not received previous NSP training. Moreover, there was an apparent reversed sex difference favoring females on some measures of spatial performance in NSP-trained rats. These results suggest that performance on the water-maze task, including the expression of sex differences, can be altered by previous familiarization with nonspatial aspects of the task.

Animals↗

Sexually dimorphic spatial learning in meadow voles Microtus pennsylvanicus and deer mice Peromyscus maniculatus.

A number of studies examining developmental, neural and hormonal aspects of sexually dimorphic spatial learning (Morris water-maze) in meadow voles (Microtus pennsylvanicus) and deer mice (Peromyscus maniculatus) are described. We found that, in adult deer mice, female spatial performance decreased during the breeding season relative to the non-breeding season, whereas the reverse pattern was observed in male performance. There was a sex difference favouring males in spatial learning during the breeding season, but not during the non-breeding season. In adult meadow voles, females with low levels of oestradiol and males performed better in the water-maze than females with high levels of oestradiol. Postweaning voles (20 and 25 days after birth) acquired the water-maze task more quickly than preweaning voles (day 10). No sex difference in water-maze performance was evident at any of these juvenile ages. When these same voles were tested again as adults to investigate retention and re-acquisition of the water-maze, both males and females from male-biased litters re-acquired the task better than males and females from female-biased litters. Together, the results of these studies indicate that sexually dimorphic spatial ability is dependent on the organization (in utero) and activational effects of gonadal hormones. These studies provide the first demonstration of the influence of natural changes in reproductive status on spatial learning of deer mice and meadow voles. The results also demonstrate that spatial performance of males and females is differentially affected by changes in reproductive status and that group differences in the laboratory are associated with group differences in space utilization in the wild. These findings help to clarify previous apparently contradictory findings about sex differences in spatial ability.

Animals↗

Area postrema mediates the formation of rapid, conditioned palatability shifts in lithium-treated rats.

The rapid acquisition and subsequent retention of lithium-induced conditioned changes in taste reactivity responses to sucrose were examined in rats with the area postrema (AP) either ablated or intact. On 2 conditioning days, a series of brief intraoral sucrose infusions was paired with the effects of LiCl or NaCl injections. Repeated associations of the sucrose taste with the effects of lithium significantly reduced ingestive responses and increased aversive responses only in the AP-intact group. AP-ablated rats treated with LiCl and rats injected with NaCl displayed an ingestive pattern of responses. Only the AP-intact rats, previously injected with LiCl, subsequently displayed evidence of a conditioned taste aversion. We conclude that toxin activation of the AP is required to produce the conditioned shift in taste reactivity responses and subsequent expression of a taste aversion in rats treated with lithium.

Animals↗

Gonadal hormone levels and spatial learning performance in the Morris water maze in male and female meadow voles, Microtus pennsylvanicus.

The present study examined the relationships between spatial learning and circulating levels of plasma estradiol and testosterone in adult male and female meadow vole, Microtus pennsylvanicus. Meadow voles are induced ovulators and most females that are housed with females or in isolation are in constant diestrus, whereas most females that are housed with males are in constant behavioral estrus. In this study sexually mature, adult male and female meadow voles housed with either females (constant diestrus) or males (constant behavioral estrus) were required to learn the spatial position of a hidden, submerged platform in the Morris water maze. Individual voles were tested using two blocks of four trials twice a day for 3 days for a total of six blocks. Task retention was examined with a probe trial 1 day after the last acquisition trial. Females were divided into two groups based on the median level of plasma estradiol [High Estradiol (15.79 +/- 1.20 pg/ml) and Low Estradiol (6.22 +/- 2.79 pg/ml) Females]. Males were similarly divided on the basis of median plasma testosterone levels [High (2.53 +/- 0.96 ng/ml) and Low Testosterone (0.45 +/- 0.08 ng/ml) Males]. High Estradiol females exhibited significantly longer latencies to reach the hidden platform, indicating poorer acquisition, than did either males (P = 0.025) or Low Estradiol females (for Blocks, 2, 3, 4, and 6, P = 0.037). Male superiority in spatial learning performance was evident only when High Estradiol females were compared to males. There were no significant performance differences between High and Low Testosterone males. There were also no group differences in retention, with all voles displaying significant retention of the spatial task. There was, however, a significant correlation between plasma estradiol levels in females and retention, with higher estradiol levels being associated with poorer retention. These results suggest that levels of estradiol in adult female meadow voles are significantly related to spatial learning, with low levels of estradiol being associated with better spatial learning. There was no evidence that levels of testosterone were related to spatial performance in adult male meadow voles. The results suggest that estradiol may have activational effects on spatial learning in the adult meadow vole and that sex differences in spatial learning are evident only when High Estradiol females are compared to adult males.

Animals↗

Cholecystokinin reduces ingestive taste reactivity responses to water in fluid-replete but not fluid-deprived rats.

The effects of hydrational factors on the ability of cholecystokinin (CCK) to alter taste reactivity responses to intraoral water infusions was assessed in fluid-replete and fluid-deprived rats. Naive male rats were injected with CCK (8 micrograms/kg, IP), or physiological saline (1 ml/kg, IP) and taste reactivity responses elicited by brief (30 s) intraoral water infusions at 2, 4, 6, 8, and 10 min postinjection were measured. One week later and following a 24 h water deprivation period, taste reactivity responses to intraoral water infusions were measured again. Exogenous administration of CCK was found to produce a significant decrease in the frequency of ingestive responses accompanied by a significant increase in passive drip during oral water infusions in fluid-replete rats. In contrast, CCK was found to have no effect on the frequency of taste reactivity responses when rats were subjected to a period of water deprivation. These results demonstrate that the rat's state of hydration interacts with the ability of CCK to alter taste reactivity responses to intraoral water infusions.

Animals↗

A multivariate assessment of spontaneous locomotor activity in the Mongolian gerbil (Meriones unguiculatus): influences of age and sex.

A multivariate assessment of the spontaneous locomotor activity of male and female Mongolian gerbils (Meriones unguiculatus) was obtained using a Digiscan automated animal activity monitoring system. Spontaneous motor activity data were collected over 1 h (5-min samples) for groups of male and female gerbils ranging from 26-341 days of age (26, 38, 62, 116, 151, 172, 196, 247, and 341). Variables examined included: total distance travelled, average distance per movement, average speed, number of horizontal movements, time in horizontal movement, time per horizontal movement, number of vertical movements, time in vertical movement, and time per vertical movement. Age had a significant effect on spontaneous activity; all measures of horizontal activity increased from preadulthood (26 and 38 days) and remained relatively constant thereafter for adults (62+ days). Vertical activity (rearing) measures were found to increase from the 62-day-old group to the 151- and 172-day-old groups and then decrease among the older groups (196+ days). Across the 12 samples, within sessions, all horizontal and vertical activity measures (except average speed) declined for both males and females. Habituation was more rapid for the preadults than for the adults on all horizontal measures except average distance per movement. No consistent sex differences in locomotor activity were found.

Aging↗

Toxin-induced conditioned changes in taste reactivity and the role of the chemosensitive area postrema.

Conditioned taste avoidances (CTAs) are an important component of behavioral regulation of ingestion. In the laboratory CTAs can be produced by pairing a novel taste stimulus with the physiological feedback produced by a toxin, such as lithium. Such toxins putatively activate a chemosensitive brainstem structure, the area postrema, which ultimately results in the production of a CTA. The present review describes a series of studies which examined conditioned changes in taste reactivity responses (TRRs) when a novel intraoral sucrose taste was paired with the effects of an intraperitoneal (IP) injection of LiCl, and the role of the area postrema in the formation of conditioned palatability shifts. It was first of all necessary to examine the effects of area postrema ablations on TRRs to a range of intraoral sucrose and quinine stimulus intensities. In the first study area postrema lesioned rats exhibited concentration dependent changes in TRRs to these taste stimuli that were very similar to those exhibited by sham lesioned rats. The second study demonstrated that 30 s intraoral infusions of sucrose (0.3 M), presented at 5 or 10 min intervals following an IP injection of LiCl (3.0 meq), resulted in conditioned changes in TRRs. These were characterized by orderly, gradual reductions in ingestive responses and increases in aversive responses. Finally, when area postrema lesioned rats (Study 3) were subjected to this conditioning procedure (brief sucrose presentations paired with the effects of LiCl) no evidence for conditioned or unconditioned changes in TRRs to sucrose were obtained. Lesioned rats injected with LiCl behaved similarly to sham lesioned rats injected with NaCl. These series of studies provide evidence indicating that the chemosensitive area postrema mediates the formation of conditioned palatability shifts induced by treatment with a toxin such as lithium.

Animals↗

Possible mechanisms by which extremely low frequency magnetic fields affect opioid function.

Although extremely low frequency (ELF, < 300 Hz) magnetic fields exert a variety of biological effects, the magnetic field sensing/transduction mechanism (or mechanisms) remain to be identified. Using the well-defined inhibitory effects that magnetic fields have on opioid peptide mediated antinociception or "analgesia" in the land snail Cepaea nemoralis, we show that these actions only occur for certain frequency and amplitude combinations of time-varying sinusoidal magnetic fields in a manner consistent with a direct influence of these fields. We exposed snails with augmented opioid activity to ELF magnetic fields, which were varied in both amplitude and frequency, along with a parallel static magnetic field. When the peak amplitude (0-547 microT) of a magnetic field of 60 Hz was varied systematically, we observed a nonlinear response, i.e., a nonlinear reduction in analgesia as measured by the latency of a defined response by the snails to a thermal stimulus. When frequency (10-240 Hz) was varied, keeping the amplitude constant (141 microT), we saw significant inhibitory effects between 30 and 35 Hz, 60 and 90 Hz and at 120 and 240 Hz. Finally, when the static field was varied but the amplitude and frequency of the time-varying field were held constant, we observed significant inhibition at almost all amplitudes. This amplitude/frequency "resonance-like" dependence of the magnetic field effects suggests that the mechanism (or mechanisms) of response to weak ELF fields likely involves a direct magnetic field detection mechanism rather than an induced current phenomenon. We examined the implications of our findings for several models proposed for the direct sensing of ELF magnetic fields.

Analgesia↗

Performance (re-acquisition) of a water-maze task by adult meadow voles: effects of age of initial task acquisition and in utero environment (litter sex-ratio).

Previous research in this laboratory has shown that preweaning and postweaning juvenile meadow voles, Microtus pennsylvanicus, can acquire a spatial task, the Morris water-maze task. The present study examined the influence of age of juvenile acquisition ("before weaning" (BW; Day 10 and 15 after birth) and "after weaning" (AW; Day 20 and 25 after birth)) of a spatial task on subsequent re-acquisition of the same hidden-platform spatial water-maze task. This study also compared sex differences and litter sex-ratio effects on reacquisition performance. Fifteen litters of adults were re-tested in the same water maze 6 weeks after being initially tested as juveniles. All analyses were conducted using a covariate that removed the group differences in the original task performance. Adult voles from female-biased litters, that had previously learned the task at an older juvenile age (AW), reacquired the same task faster than adults that had previously learned the task at a younger juvenile age (BW). In the adult BW group there was also a significant litter sex-ratio effect such that voles born into a female-biased litter re-acquired the task more slowly than did voles born into a male-biased litter. There were no significant sex or litter sex-ratio effects on spatial learning in the AW group. These results show that adult meadow voles can require a spatial task more quickly if they initially learned the task at an older juvenile age, suggestive of a period of infantile amnesia. In addition, these results indicate that the litter sex-ratio can affect adult spatial performance, suggesting that the relative amount of androgens in utero may influence the development of sexually-dimorphic spatial ability in adulthood.

Androgens↗