Biomedical subjects

S Hogg

Publications and source records attributed to S Hogg.

At least 19 recordsLinked to original sources

PubMed2000

Involvement of hippocampal neuropeptide Y in mediating the chronic actions of lithium, electroconvulsive stimulation and citalopram.

Neuropeptide Y (NPY) has been considered to be involved in the pathogenesis of affective disorders, and chronic treatment with lithium or electroconvulsive stimuli (ECS) has been shown to increase mRNA and peptide levels of NPY in rat brain tissue. Consequently, parameters reflective of NPYergic neurotransmission were studied in the hippocampus of rats following chronic treatment with lithium, ECS or the selective serotonin re-uptake inhibitor (SSRI), citalopram. Lithium (28 days, diet) and ECS (10 days, once daily) treatments caused a marked increase in levels of preproNPY mRNA in the CA1 area and dentate gyrus (DG). This increase was accompanied by an increase in extracellular levels of NPY in the dorsal hippocampus of freely moving rats as determined by microdialysis, suggesting that lithium and ECS treatments lead to an increased biosynthesis and release of NPY in this area. (125)I-peptide YY (PYY) binding was reduced by 40 and 60% respectively in the DG following the same treatments, showing that the increased release is accompanied by a down-regulation of corresponding binding sites. In contrast, citalopram (10 mg/kg i.p., twice daily for 28 days) caused a 100% increase in (125)I-PYY binding in CA, CA3 and DG while levels of preproNPY mRNA and extracellular NPY in the hippocampus were unaffected. The results indicate that various agents and stimuli exerting antidepressant effects in humans, such as chronic lithium, ECS and citalopram all increase NPYergic neurotransmission in the hippocampus by distinct modes of action. Moreover, NPY (6 microg) given intracerebroventricularly (i.c.v.) induced an antidepressant-like effect in the forced swim test. It is hypothesised that the increase in NPYergic neurotransmission may be associated with the mechanism of action of various antidepressant treatments in the alleviation of depression.

Animals↗

PubMed1999

Behavioural consequences of repeated social defeat in the mouse: preliminary evaluation of a potential animal model of depression.

The behavioural consequences of repeated social defeat, coupled with the stress of continuously living opposite a dominant animal, were assessed in male NMRI mice. The method adopted here differed from the previously published techniques in that the physical element of the social defeat procedure was reduced to a minimum. The subordinate animals consistently weighed less than control animals, and displayed a reduced number of visits to the partition compared to the dominant animals, which has previously been used as a marker of social behaviour. The subordinate animals did not show any differences in the amount of ethanol solution consumed compared to controls, and did not display an increase in immobility time measured in the forced swimming test. The subordinate animals did, however, display anxiogenic-like behaviour as indicated by an increased aversion of the light section of the black/white test box, which was partially reversed by chronic treatment (3weeks; 20mg/kg/day) with the antidepressant, citalopram. Decreased exploration by the subordinate animals in the black/white test box was also observed, which was reversed by chronic citalopram treatment. It is suggested that, whilst the model requires further validation, it may be a useful approach for the study of antidepressant compounds.

Aggression↗

PubMed1998

Mild traumatic lesion of the right parietal cortex in the rat: characterisation of a conditioned freezing deficit and its reversal by dizocilpine.

We have previously demonstrated that traumatic injury of the lateral aspect of the right parietal cortex results in reduced acquisition of the passive avoidance task but enhanced learning in an active avoidance procedure. In order to try to explain the apparent dichotomy between these findings a series of experiments examined the effect of fluid percussion-induced traumatic brain injury (FP-TBI) on the conditioned freezing response to a context previously paired with an aversive stimulus. Rats subjected to FP-TBI displayed less conditioned freezing than the sham-operated controls. This effect was particularly marked when the delay between context exposure and footshock was short (< or = 30 s) and was no longer significant when this delay was 3 min, indicating that the injured animals did not have an impaired freezing response per se. This phenomenon was enduring such that it could still be observed 2 months following the surgery. There was no significant freezing deficit after FP-TBI of the motor cortex, demonstrating that the site of injury is important and that the freezing deficit is not a general response to CNS trauma. The NMDA receptor antagonist dizocilpine (MK-801, 1 mg/kg i.v.) significantly reduced the trauma-induced freezing deficit when administered as a single bolus 15 min prior to the surgery, or as three repeated treatments (3 x 0.33 mg/kg) 15 min, and 6 and 24 h following lesion. The trauma-induced deficit in conditioned freezing can explain the differences in active and passive avoidance behaviours and appears to be specific to lesion of the lateral parietal cortex. In addition, the behavioural deficit can be attenuated using the neuroprotective agent dizocilpine, suggesting that it may prove useful as a sensitive and specific measure of cortical damage following traumatic injury.

Animals↗

PubMed1998

Mild traumatic lesion of the right parietal cortex of the rat: selective behavioural deficits in the absence of neurological impairment.

Fluid impact models are widely used to study the histological and neurochemical consequences of traumatic brain injury and although behavioural consequences have also been studied, behavioural changes are often confounded by non-specific neurological deficits. In the present study we investigated behavioural effects of a unilateral mild traumatic lesion of the right lateral parietal cortex. This region is implicated in a number of basic and complex behaviors, and we therefore analyzed the performance of rats in a diverse range of behavioural procedures. The lesion had no effects on general neurological function, motor activity (activity boxes, rota-rod and paw reaching tests), habituation to a novel environment (holeboard), spatial learning ability (Morris water maze) or anxiety (elevated plus-maze). However, the lesioned animals demonstrated lower levels of exploration than the control group when novel objects were placed beneath some of the holes in the holeboard. Lesioned animals also differed from controls in their performance in passive and active avoidance procedures. In a step-through passive avoidance test the lesioned rats performed worse than the sham-operated controls, i.e. they had significantly lower entry latencies on the 2nd day. In contrast, in the active avoidance task the lesioned animals performed better than sham-operated rats, demonstrating a better ability to learn to avoid and escape from the shock. These diverse results in different tests of learning and memory, in particular the impairment in passive avoidance and the improvement in active avoidance behavior, are difficult to reconcile with a simple effect of the lesion on cognitive performance per se. The complete absence of general neurological deficits following the mild traumatic injury rules out the possibility that the observed behavioural changes reflect a non-specific impairment. These results demonstrate that mild traumatic lesion of the right parietal cortex can induce relatively selective behavioural changes that may serve to study functional recovery after trauma. However further work is required to establish the underlying deficit(s) that has led to the behavioural effects described here.

Animals↗

PubMed1998

Neuroprotective effect of eliprodil: attenuation of a conditioned freezing deficit induced by traumatic injury of the right parietal cortex in the rat.

We have previously demonstrated that a lateral fluid percussion-induced traumatic lesion of the right parietal cortex can lead to a deficit in a conditioned freezing response and that this deficit can be attenuated by both pre- and postlesion administration of the NMDA receptor antagonist dizocilpine. In the present study, we investigated the effects of eliprodil, a noncompetitive NMDA receptor antagonist acting at the polyamine modulatory site, which also acts as a Ca2+ channel blocker, on the trauma-induced conditioned freezing deficit. Eliprodil produced a 50% reduction in this deficit when administered as three 1 mg/kg injections i.v. at 15 min, 6 h, and 24 h following the lesion. Approximately the same degree of protection was afforded when 2 x 1.5 mg/kg were administered 6 and 24 h and equally at 12 and 24 h after surgery (56% and 59%, respectively). A single treatment (3 mg/kg) at 24 h was ineffective against the deficit. The protection afforded with treatment at 6 and 24 h after lesion was dose dependent, with a minimal active dose of 2 x 0.75 mg/kg. These data complement those previously published on the ability of eliprodil to reduce lesion volume following traumatic brain injury and show, in addition, that the neuroprotective effect has functional consequences.

Analysis of Variance↗

PubMed1997

Changes in tonic immobility and the GABA-benzodiazepine system in response to handling in the chick.

Changes in the GABA-benzodiazepine system were investigated following regular handling of male chicks. Compared with handling-naive chicks, those exposed to 10 days of gentle handling required a larger number of inductions and had a lower duration of tonic immobility. Corresponding biochemical changes occurred, with handling-habituated chicks having a significantly lower basal [14C]GABA release from archistriatal slices and a reduction in the Bmax of [3H]muscimol binding in the forebrain. Benzodiazepine binding in the archistriatum was investigated using in vitro quantitative receptor autoradiography. Binding was localised in the anterior, mediale, dorsalis, and ventralis intermedium nuclei of the archistriatum, and there was significantly more binding in the anterior and ventralis intermedium/mediale archistriatum nuclei than in the dorsalis intermedium archistriatum nuclei. Benzodiazepine binding was not altered after handling in any of the investigated nuclei of the archistriatum. The results suggest that whereas several days of gentle handling in chicks leads to a decrease in forebrain GABAA receptors and a decrease in GABA release from the archistriatum, there are no accompanying changes in benzodiazepine receptors. Regular handling exerts a specific effect on chicks: it reduces their fear or human beings but not that of novel places or objects. It is possible that the pattern of biochemical changes observed in the present study may be specifically associated with this particular behavioural modification rather than with a change in general fearfulness.

Animals↗

PubMed1996

Differences in benzodiazepine binding in quail selectively bred for differences in tonic immobility.

We have previously found that quail selectively bred to exhibit long (LTI) or short (STI) tonic immobility responses to manual restraint differed with respect to the affinity of binding at the diazepam-sensitive benzodiazepine binding site. In the current study, binding at other components of the GABAA-benzodiazepine receptor complex was investigated. Whereas the lines did not differ in either number or affinity of GABAA receptors, we found that GABA caused significantly greater enhancement of [3H]flunitrazepam binding in the forebrains of LTI than in STI birds. There was also significantly higher binding to the diazepam-insensitive component (alcohol binding site) of the GABAA-benzodiazepine complex in the forebrain of the LTI line. It is not known, however, whether this difference in the lines is due to differences in number or affinity of these sites. It is discussed whether these manifold differences between the lines in binding at the forebrain sites of the GABAA-benzodiazepine complex could be founded on subunit differences, and whether differences in benzodiazepine binding could underlie the genetically determined behavioural differences in tonic immobility.

Animals↗

PubMed1996

A review of the validity and variability of the elevated plus-maze as an animal model of anxiety.

Despite or possibly by virtue of the fact that it is one of the most commonly used animal models of anxiety the Elevated Plus-Maze (EPM) results in a wide range of, often contradictory, results following pharmacological experiments. The responses from a questionnaire distributed to 65 groups that have published studies using the EPM in the past 3 years has, along with reference to published reports, enabled some conclusions regarding the influencing factors to be drawn. Some evidence for differential sensitivities between strains exists, with albino rats being more sensitive to the anxiolytic effects of 5-HT3 receptor antagonists and 5-HT1A receptor agonists than pigmented animals. Most important, however, is the manipulation of the animals prior to testing and the aversiveness of the test conditions themselves. Stressing animals before testing (e.g., by moving from holding to test room) or using more aversive test conditions (e.g., elevated light levels) increases sensitivity to potential anxiolytics. Animals that are habituated to gentle handling or tested in less aversive conditions (e.g., EPM with ledges) show reduced likelihood of anxiolytic responses with administration of 5-HT3 antagonists, 5-HT1A agonists, and benzodiazepines.

Animals↗

PubMed1996

Behavioural and neurochemical responses of male and female chicks to cat odour.

In the first experiment male chicks were exposed to neutral and cat odours at days 4, 7, or 10 after hatching. Of the chicks tested at day 4, few made contact with either odour cloth, but those tested at day 7 made fewer contacts with the cat odour cloth, compared with the neutral odour, spent less time in contact with it, and spent more time in the zone furthest from the cloth. These clear differences were not seen in the group tested at day 10. In a second experiment, the behaviour of day 7 male chicks was compared in the presence of neutral, disinfectant, chick blood or cat odours, and the most extreme differences were between neutral and cat odours. In a third experiment, both male and female chicks were exposed to cat odour at day 7 and both showed similar avoidance. After exposure to cat odour both sexes showed significantly reduced GABA enhancement of benzodiazepine binding; which is a change associated with increased fear. However, after exposure to cat odour, they also showed significant decreases in 5-HT availability evidenced by lower basal and K(+)-evoked [3H]-5-HT release and, in the male chicks only, by an increased [3H]-5-HT uptake from archistriatal slices. These changes in 5-HT function are in the direction associated with reduced fear and would, therefore, seem to be adaptive and compensatory in function. Neither male nor female chicks showed any differences in [14C]-GABA release or uptake as a result of exposure to cat odour. Although the pattern of response to cat odour was the same in both male and female chicks at day 7, there were significant sex differences in 5-HT and GABA tone and benzodiazepine binding; these sex differences were also found in day 10 chicks. The importance of these for sex differences in trait anxiety is discussed.

Animals↗

PubMed1994

5-HT1A receptors in the median raphe nucleus and dorsal hippocampus may mediate anxiolytic and anxiogenic behaviours respectively.

The behavioural response of rats in the high light unfamiliar condition of the social interaction test of anxiety was observed following direct administration of the 5-HT1A receptor agonist, (+/-)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT, 50, 100 or 200 ng) or antagonist tertatolol (3 micrograms) into the median raphe nucleus or dorsal hippocampus. In the median raphe nucleus, 8-OH-DPAT (200 ng) significantly increased social interaction without changing locomotor activity; lower doses were inactive. In the dorsal hippocampus, bilateral injection of 8-OH-DPAT (100 ng) significantly decreased social interaction, without effect on locomotor activity; both 50 and 100 ng significantly changed grooming. Tertatolol had no effect on social interaction following administration to the median raphe nucleus, but significantly increased locomotor activity. Bilateral injection of tertatolol into the dorsal hippocampus decreased social interaction and changed grooming. These effects are similar to those of 8-OH-DPAT suggesting tertatolol may have 5-HT1A receptor agonist properties. In conclusion, the findings of this study demonstrate that 5-HT1A somatodendritic autoreceptors and post-synaptic receptors mediate anxiolytic and anxiogenic effects, respectively, in the social interaction test.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1994

Regional differences in rat benzodiazepine binding in response to novelty and cat odour.

Laboratory rats exhibit innate behavioural and corticosterone responses when exposed to cat odour. However, not all are responsive and differences in benzodiazepine receptor binding between responders and non-responders were explored. Rats were exposed to cat odour for 5 min and based on time spent sheltering were divided into responders (n = 21; mean +/- SEM = 244 +/- 8.2 sec) or non-responders (n = 20; 43.9 +/- 4.8 sec). Four days later, both groups were randomly allocated among 3 experimental conditions: home-cage, neutral or cat odour, and killed 30 min after exposure. [3H]flunitrazepam binding was performed at two ligand concentrations (2 and 10 nM); where significant differences in single point binding were found, Scatchard analysis was performed on pooled samples. In hippocampus and frontal cortex responders had significantly lower binding than non-responders. In hippocampus this was most apparent when the rats were exposed to the novel test situation, i.e. neutral odour and was due to a reduction in affinity (Kd = 0.4 and 1.2 nM non-responders and responders). In frontal cortex, differences were significant only following exposure to cat odour (Bmax = 2663 and 1501 fmol/mg protein in non-responders and responders). The changes in amygdala were not significant.

Amygdala↗

PubMed1994

Receptor binding in Japanese quail selected for long or short tonic immobility.

Japanese quail, selectively bred for long (LTI) and short (STI) tonic immobility (TI) responses, are thought to represent high and low fear groups, respectively. To study the neurochemical mechanisms underlying the behavioral distinctions, binding parameters were determined at the benzodiazepine, 5-HT1A, 5-HT3, alpha 2, and opioid receptor sites in the forebrains of the two lines. No differences were found in 5-HT1A, 5-HT3, alpha 2, mu- or kappa-opioid receptor binding between the lines. The KD for the binding of [3H]-flunitrazepam at the benzodiazepine receptor was significantly greater in the LTI than in the STI birds, indicating lower affinity for benzodiazepine ligands. The lines did not differ in benzodiazepine receptor number. Using [3H]-naltrindole, the LTI line was found to have fewer delta-opioid receptors than the STI line; the birds did not vary with respect to the affinity of these receptors. Thus, the selective breeding of the two lines has resulted in differences in benzodiazepine and delta-opioid binding, and these could produce differences in activity levels, fear, and pain responses, all of which could contribute to the tonic immobility response.

Animals↗

PubMed1994

Responders and nonresponders to cat odor do not differ in other tests of anxiety.

Laboratory-bred rats can be divided into those showing clear innate behavioral responses to the odor of a predator (a cat) and those showing no response. However, these two groups did not differ in their responses to a neutral odor, or in the social interaction or elevated plus-maze tests of anxiety. This suggests a distinction between phobic anxiety (generated by cat odor) and a generalized anxiety state (generated by novelty in the other tests). Trial 2 in the plus-maze generates a state of fear that is distinct from that generated on trial 1, and one suggested to reflect phobic anxiety. Although the groups of cat responders and nonresponders did not differ in their scores on trial 2 in the plus-maze, two clear groups of responders and nonresponders could be identified on this trial (but not on trial 1 or in the social interaction test). This suggests that it is possible to identify bimodal populations of rats in tests of both innate and acquired simple phobias.

Animals↗

PubMed1990

Validity and reproducibility of a screening examination for neurological abnormality in persons exposed to methylmercury.

The validity and reliability of methods of screening for neurologic abnormality were assessed as part of an investigation of an outbreak of methylmercury exposure in two northern Canadian communities. Four hundred and forty-five Cree Indians were examined by one of five neurologists in a complete neurologic examination and by a trained paramedical observer in a short screening examination which included a selection of tests from the complete examination. The screening examinations were recorded on videotape and those for 176 men were reviewed by the five neurologists and the paramedical observer 1 year after the field studies. The prevalence of abnormality assessed in the field screening examination was greater than that assessed during the complete neurologic examination, for neurologic features included in both examinations. However, agreement between examinations in identifying individuals with abnormality was poor with the sensitivity of the screening examination falling under 50% for half of the neurologic features examined. In contrast, specificity was over 80% for 14 of 18 features. Review of the videotapes revealed marked interobserver variation in the assessment of the prevalence of neurologic abnormality and poor agreement with the neurologic examinations in the identification of abnormality in individuals, with kappa less than 0.2 for most neurologic features. The levels of agreement between the neurologic examinations and the screening examinations conducted in the field and by videotape review suggest that neither screening examination provides equivalent information in the identification of the presence of abnormality to that obtained in the neurologic examination.

Female↗

PubMed1988

Measurement of the clinical status of patients with breast cancer: evidence for the validity of self assessment with linear analogue scales.

We have assessed the validity of a method of measurement for describing the clinical status of patients with breast cancer. One hundred and nine patients with breast cancer assigned numerical values to their own state of health using linear analogue scales. We have shown previously that this method of measurement is reliable and corresponds well with other methods of assessment. Validity was assessed in this study by examining the ability of measurements to distinguish between groups of patients who differed either in the presence of metastatic disease or in the treatments they were receiving. All patients completed the same set of 29 linear analogue scales that enquired about the severity of health related problems and symptoms. In general, patients with metastatic disease were clearly distinguished from patients without metastases by their scores on items related to physical function. Patients receiving chemotherapy were distinguished from those not receiving chemotherapy by their scores on treatment related toxicities. Measures of psychological and social health were similar in patients receiving chemotherapy regardless of disease status. These results provide further support for the validity of measurement of clinical status with linear analogue scales scored by patients.

Breast Neoplasms↗

PubMed1986

Factor V in human vascular endothelium and in endothelial cells in culture.

Human blood vessels and human umbilical vein endothelial cells in culture were examined for the presence and synthesis of factor V. Factor V antigen was detected on the luminal surface of blood vessels washed with buffers containing calcium but was absent from segments of the same vessels perfused with buffers containing EDTA. Very low levels of endogenous factor V antigen were found in endothelial cells in culture but these cells did not synthesise factor V in sufficient quantities to be detected by the present methods. Factor V activity was not detected in any of the present cell preparations.

Adult↗

PubMed1986

The relationship between von Willebrand factor antigen and fibronectin in human plasma, endothelial cells and fibroblasts in culture.

The distribution of von Willebrand factor antigen (vWFAg) and fibronectin (Fn) in endothelial cells and in fibroblasts in culture was examined using immunohistological methods. Extracellular matrices were studied after removal of cells by mild hypotonic lysis. Co-distribution of these antigens was also examined after culture of fibroblasts in the presence of endothelial cell conditioned medium or of exogenous vWFAg. The presence of intracellular vWFAg and its association with extracellular Fn in confluent endothelial cells was confirmed. Furthermore, both antigens were detected in matrices from fibroblasts grown in the presence of human plasma and endothelial cell medium. vWFAg was not found, however, in the absence of endothelial cell conditioned medium or in experiments using human serum in place of plasma. Cross-linking of vWFAg was examined using quantitative and qualitative electrophoretic methods. Levels of vWFAg in serum from patients with severe Haemophilia A were approximately 50% of those found in the corresponding plasma. Furthermore, vWFAg was reduced to similar levels in serum from normal blood to which heparin was added. The lowest levels of vWFAg were found in the presence of sufficient heparin to totally inhibit the formation of fibrin. In contrast, levels of Fn remained unchanged in these circumstances. The results did not support the view that vWFAg was cross-linked to Fn in plasma by thrombin-activated factor XIII. In addition, immunoelectrophoresis of cultured endothelial cell products did not demonstrate cross-linking of vWFAg to Fn. The data are consistent with the concept that deposition of vWFAg on the subendothelium is dependent on viable endothelial cells or on another product of these cells.

Blood Coagulation↗

PubMed1986

Measurement of serum DNA binding in chronic active hepatitis and systemic lupus erythematosus using the Farr assay.

Antibodies to double-stranded DNA (dsDNA), generally regarded as highly specific for systemic lupus erythematosus (SLE), have also been reported in chronic active hepatitis (CAH). Using the Farr assay and E. coli DNA, fractionated by benzoylated-naphthoylated-DEAE cellulose chromatography into dsDNA and dsDNA containing single-stranded regions, we compared the serum DNA binding of CAH and SLE patients. Although CAH sera were found to have dsDNA binding significantly above the normal control group such binding was of low level and we could find no evidence of markedly elevated dsDNA binding in CAH. However 12 of the 20 CAH sera studied did bind preferentially to dsDNA containing single-stranded regions suggesting the presence of anti-single-stranded DNA antibodies. We conclude that the description of elevated anti-dsDNA antibodies, as measured by the Farr assay, in CAH is due to the interaction of anti-single-stranded DNA antibodies or other serum components with single-stranded DNA contaminating dsDNA preparations.

Adult↗