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Biomedical subjects

K P Ossenkopp

Publications and source records attributed to K P Ossenkopp.

At least 19 recordsLinked to original sources

Rotation-induced conditioned rejection in the taste reactivity test.

The taste reactivity test was used to evaluate the ability of motion sickness to produce conditioned rejection reactions, a putative measure of nausea in rats. Following three conditioning trials, rats displayed conditioned rejection reactions during an intraoral infusion of a rotation-paired saccharin solution. This is the first demonstration of conditioned rejection produced with a non-pharmacological emetic agent and provides support that the conditioned rejection reaction may serve as a rat model of nausea.

Animals

Brief predator odour exposure activates the HPA axis independent of locomotor changes.

Although predator exposure has been proposed to elicit both behavioural responses and neuroendocrine effects in rodents, results of an increasing number studies have failed to consistently detect both of these alterations. We provide a detailed multivariate quantitative assessment of locomotor activity levels and plasma levels of adrenocorticotrophic hormone (ACTH) and corticosterone of male and female laboratory rats following brief (5 min) exposure to a predator odour, (2-propylthietane, the main constituent of weasel anal gland secretion). We show that there is a clear distinction between the behavioural and neuroendocrine responses, with predator odour inducing significant increases in corticosterone and ACTH levels without any significant accompanying changes in various locomotor activity measures.

Adrenocorticotropic Hormone

Relations of hippocampal volume and dentate gyrus width to gonadal hormone levels in male and female meadow voles.

The present study examined hippocampal volume and dentate gyrus width and their relations to gonadal hormone levels in adult male and female meadow voles, Microtus pennsylvanicus. Females were split into High and Low Estradiol groups based on the median estradiol level. Males were similarly split into High and Low Testosterone groups. Contrary to previous reports in wild meadow voles, there was no evidence of an overall sex difference in hippocampal volume. However, when male-female comparisons were limited to High Testosterone males and Low Estradiol females a significant sex difference in hippocampal volume favouring males did emerge. Hippocampal volume in males was related to testosterone level, with High Testosterone males having significantly larger hippocampi than Low Testosterone males. Similarly, there was a significant influence of plasma estradiol level on hippocampal volume and left dentate gyrus width, with High Estradiol females having larger hippocampi and dentate gyrus width than Low Estradiol females. In addition, consistent with previous findings in the laboratory rat, there were sex differences favouring males in right dentate gyrus width. These findings show that there is a complex relationship between hippocampal volume, dentate gyrus width and gonadal hormone levels in male and female meadow voles.

Animals

Differential effects of lipopolysaccharide and cholecystokinin on sucrose intake and palatability.

The differential effects of CCK and lipopolysaccharide (LPS) on sucrose intake and palatability were examined. Rats were injected with LPS (200 microg/kg ip) or NaCl (0.9%, vehicle) and 2 h later received a second injection of either CCK (8 microg/kg ip) or NaCl. In experiment 1, sucrose (0.3 M) intake was monitored for 1 h on three different test days 72 h apart, while in experiment 2, palatability was assessed by means of the taste reactivity test (TRT) on two separate days (72 h apart). In the TRT, orofacial and somatic responses to brief (30 s) intraoral infusions of sucrose were recorded and analyzed for response frequency. Singly, LPS and CCK reduced sucrose intake, with a more pronounced effect from combined LPS and CCK. LPS by itself did not alter sucrose palatability, as evidenced by continuous high levels of ingestive responding. In contrast, CCK-treated rats displayed a pattern of responding indicative of satiety, as did the combined LPS-CCK-treated rats. These results suggest that LPS does not induce hypophagia by altering palatability.

Animals

Learning to cope with biting flies: rapid NMDA-mediated acquisition of conditioned analgesia.

A 30-min exposure to intact biting flies (stable flies) induced an opioid-mediated analgesia in fly-naive male deer mice, whereas exposure to either altered biting flies whose biting mouthparts were removed or nonbiting house flies had no significant effects. However, mice that were previously exposed to intact stable flies for 30 min exhibited significant analgesia when exposed 24-168 hr later to stable flies whose biting parts were removed, but not to nonbiting house flies. Administration of the specific N-methyl-D-aspartate (NMDA) antagonist NPC 12626 to fly-naive mice before exposure to intact flies, although not significantly reducing the analgesic response, blocked the subsequent conditioned analgesia. Naloxone, which blocked the intact biting fly-induced analgesia, did not alter the acquisition of the conditioned analgesic response to the altered stable flies. This demonstrates an NMDA-mediated acquisition of conditioned analgesia to a natural aversive stimulus.

Adaptation, Physiological

Brief exposure of mice to 60 Hz magnetic fields reduces the analgesic effects of the neuroactive steroid, 3alpha-hydroxy-4-pregnen-20-one.

Relatively weak, extremely low frequency (ELF), magnetic fields have been shown to exert a variety of biological effects, although the modes of action remain to be established. Neuroactive steroids and neurosteroids have been shown to produce a diverse range of rapid centrally mediated behavioral and physiological effects that are reported to be sensitive to magnetic fields. Here we show that brief exposure of male mice to an ELF magnetic field (30 min, 60 Hz, 141 microT peak) significantly reduces the analgesic effects arising from intracerebroventricular (i.c.v.) administration of the centrally produced allylic neuroactive steroid, 3alpha-hydroxy-4-pregnen-20-one (3alphaHP) and that the dihydropyridine (DHP) calcium channel antagonists, diltiazem and nifedipine, block the inhibitory effects of the 60 Hz ELF on 3alphaHP-induced analgesia. These results indicate that exposure to 60 Hz ELF affects the analgesic effects of neuroactive steroids such as 3alphaHP through alterations in calcium channel function. These findings raise the possibility that ELF magnetic fields may, in part, exert their actions through effects on diverse neuroactive steroid modulated processes.

20-alpha-Dihydroprogesterone

Individual differences in radial maze performance and locomotor activity in the meadow vole, Microtus pennsylvanicus.

Individual differences in the radial maze performance and locomotor activity of wild-caught and first-generation laboratory-born meadow voles are described. Based on their patterns of response in an eight-arm radial maze the essentially wild voles fell into three behavioral categories: 1) strict algorithmic (i.e., they systematically chose the next adjacent arm to their previous choice); 2) nonalgorithmic (i.e., they ran the maze without any consistent or definable pattern); and 3) nonrunners (i.e., nonperformers of the task who remained relatively immobile in the arms of the maze). The algorithmic and nonalgorithmic voles further differed in their responses to an interference manipulation of the radial maze task. Algorithmic individuals displayed a marked performance deficit, while the nonalgorithmic individuals showed minimal disruption to a 1-min delay interruption of the maze task. Measurements of several aspects of locomotor activity using the automated Digiscan activity monitoring system revealed that the algorithmic individuals also displayed significantly greater levels of activity than the nonalgorithmic or nonrunners, with no significant difference in activity between the latter two groups. These findings suggest that the algorithmic voles were relatively inflexible in their behavior, while the nonalgorithmic individuals were more flexible in their maze performance and likely in their use of spatial and nonspatial information. These individual differences in laboratory measures of learning behavior and locomotor activity in meadow voles are consistent with the polymorphism that is proposed to occur in the wild.

Animals

Sex differences in spontaneous locomotor activity and rotational behavior in meadow voles.

Sex differences in rotational behavior have been most clearly established in laboratory rats with females exhibiting a turning bias. Here, using an automated open-field apparatus, locomotor activity and spontaneous rotational behavior were examined in diurnally crepuscularly active reproductive male and female meadow voles (Microtus pennsylvanicus). Meadow voles, being induced ovulators, permitted analysis of females in constant behavioral estrous. Males displayed significantly greater levels of activity and also significantly greater levels of clockwise but not counterclockwise rotational behavior relative to the females. Rotational behavior was less strongly related to activity levels in female as compared to male voles. In addition, females displayed an overall turning bias. These results contrast with findings from laboratory rats in which females are reported to display greater levels of both locomotor activity and rotational behavior. They are, however, consistent with the rotational bias evident in female rats. The present findings confirm the presence of sex differences in rotational behavior and indicate that factors other than activity levels are involved in the generation and/or expression of these sex differences. Sex differences in anxiety and routine-like behavior (i.e., asymmetry in movement) are discussed as possible factors contributing to these male-female differences in rotational behavior.

Animals

Sex differences in spatial learning and prefrontal and parietal cortical dendritic morphology in the meadow vole, Microtus pennsylvanicus.

The prefrontal and parietal cortex has been implicated in the mediation of spatially related behaviors in male and female laboratory rats. Meadow voles, Microtus pennsylvanicus, are diurnally-crepuscularly active microtine rodents that exhibit a variety of sexually dimorphic spatially associated behaviors in both the laboratory and wild. In the present study we examined both the spatial Morris water maze performance and dendritic architecture and branching of neuronal cells in the prefrontal and parietal cortex of reproductive male and female meadow voles. Males learned the location of the hidden platform in the water task faster than estrous females and on probe trials they spent more time in the previously correct quadrant than females. Dendritic analysis with Golgi-Cox stained sections showed that male voles had significantly more dendritic arborization in the medial prefrontal and parietal cortex than females. These sex differences in both spatial navigation ability and in neural structures related to spatial navigation in meadow voles suggest that the size of neural areas might be shaped by ecological pressures associated with sexually dimorphic spatial behaviors.

Animals

Plasma testosterone levels are related to various aspects of locomotor activity in wild-caught male meadow voles (Microtus pennsylvanicus).

The relationship between plasma testosterone levels and locomotor activity in wild-caught sexually mature male meadow voles (Microtus pennsylvanicus) was assessed in the laboratory. Several aspects of locomotor activity were monitored for 1 h on two consecutive days using the automated Digiscan activity monitoring system. Plasma testosterone levels were determined immediately following the second day of activity monitoring. Significant Pearson correlations were obtained between plasma testosterone levels and total distance traveled [r(10) = 0.55, p < 0.05] and amount of time spent in movement [r(10) - 0.55, p < 0.05] on the second day. The wild voles showed a reduction in activity levels from the first to the second day of activity monitoring, which is indicative of habituation to a novel environment. This study provides direct evidence for a significant correlation between laboratory measures of behavioral activity and plasma testosterone levels in a wild-caught rodent. These findings indicate that previous assessments of hormone-behavior relationships in laboratory-bred rodents are consistent with the relationship between hormones and behavior in wild rodents.

Activity Cycles

Analgesic effects of a specific pulsed magnetic field in the land snail, Cepaea nemoralis: consequences of repeated exposures, relations to tolerance and cross-tolerance with DPDPE.

It has been demonstrated previously that a short acute exposure to a specific extremely low frequency pulsed magnetic field (Cnp) can induce significant partly opioid-mediated analgesia in the land snail, Cepaea nemoralis. Here, this Cnp-induced analgesia is examined for the development of tolerance to daily repeated acute exposures of 15 or 30 min duration. Acute cross-tolerance to the delta opioid receptor directed agonist DPDPE, [D-Pen2, D-Pen5]enkephalin, was also found. Before (pre-exposure) and after (0, 15, 30 and 60 min) exposure to either a sham or Cnp magnetic field, snails were tested for an aversive reaction to a warmed surface (40 degrees C), and the latency time to the aversive reaction was recorded. Snails that were exposed to the Cnp showed a significant increase in the latency time (F1.55 = 2856.4; p < 0.001; Eta2 = 0.95), which may be interpreted as an induction of analgesia. During the daily (9 day) repeated acute exposures, the induction of analgesic response was significantly reduced, but not ablated. Altering the environmental conditions of the Cnp exposure restored a significant proportion of the partly developed tolerance, consistent with previous reports of environmental specificity in the development of opioid tolerance. These findings suggest that the partial development of tolerance to the opioid-mediated portion of Cnp-induced analgesia may be countered by altering the specific environmental Cnp exposure conditions.

Analgesia

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