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Biomedical subjects

P F Brain

Publications and source records attributed to P F Brain.

At least 19 recordsLinked to original sources
PubMed2005

Time-dependent behavioral, neurochemical, and immune consequences of repeated experiences of social defeat stress in male mice and the ameliorative effects of fluoxetine.

This study attempted to determine whether differing numbers of days of repeated defeat experience altered behavior, immune measures, and neuroendocrine mediators in mice. OF1 male mice were socially stressed by repeated experiences of defeat in a sensorial contact model. Subjects exposed to nine defeats showed more stretch-attend postures and fewer active defense elements than counterparts exposed to 23 defeats. Submissive subjects with nine experiences of defeat also had a lower splenocyte proliferative response than unmanipulated controls. The proliferation index progressively increased but at a higher rate in manipulated controls than in socially stressed subjects, resulting in a significant immunosuppressive effect after 23 days of exposure to social stressors. Nine days of such exposure resulted in higher hypothalamic ratios of serotonin and dopamine to their major metabolites than in unmanipulated or manipulated controls and subjects socially stressed for 23 days. The data generally indicate that the acute social stressors (such as nine defeats) produce a profile of behavioral and physiological variables characteristic of a state of anxiety. The proliferation index was also lower after 52 days of social stress than in manipulated controls. Fluoxetine treatment appeared to have an anxiolytic effect, reducing immobility, and even seemed to protect subjects from the immune impairment and endocrine alteration caused by social stressors. The results generally provide clues that improve our knowledge of the consequences of social stressors and their possible treatment.

Analysis of Variance↗
PubMed2003

Endocrine and lymphoproliferative response changes produced by social stress in mice.

Daily dyadic resident-intruder encounters and uninterrupted cohabitation in pairs were used to assess the impact of different durations (5 and 15 days) of dominance and subordination experiences on splenic lymphoproliferative responses in male OF1 strain mice. HPA axis activity was assessed by measuring serum corticosterone levels, whereas splenic norepinephrine (NE) content provided a sympathetic activity index. Corticosterone levels in subordinate subjects were generally higher than in their control or dominant counterparts in both treatment paradigms. Corticosterone levels in dominant subjects were lower than in their control counterparts in both. Increasing the duration of treatments generally decreased such titers, especially so in subordinate subjects. No differences were detected in splenic NE content. Animals subjected to social interaction generally showed greater proliferation than their control counterparts. This effect was more pronounced in subordinates than dominants and after longer- rather than short-duration treatments. There was no inverse relation between proliferative responses and the subject's corticosterone levels. While corticosterone may have a general immunomodulating effect, other mediators apparently account for the effects produced by these social stress paradigms on splenic proliferative response.

Agonistic Behavior↗
PubMed2000

Steroid hormone-induced effects on membrane fluidity and their potential roles in non-genomic mechanisms.

Steroid hormones are lipophilic suggesting they intercalate into the bilayer of target cell plasma membranes, potentially altering the fluidity and function of the membrane. The present study measured the effects of steroidal exposure on both phospholipid fluidity and integral protein mobility. Studies were performed on the effects of a variety of steroids on phosphatidylcholine liposomes, synaptosomal plasma membranes and sarcoplasmic reticulum membranes. Progesterone decreased the lipid fluidity, whereas testosterone had no effect on lipid movement. The estrogen, 17 beta-estradiol, an aromatised metabolite of testosterone, increased lipid mobility. In each case, the steroid action was concentration-dependent. The steroids all increased the activity of the Ca2+ ATPase of SR membrane, in keeping with their effects on this enzyme's aggregation state. The results suggest that, although lipid fluidity is a factor influencing protein activity, their mobility within the bilayer is the primary determinant of enzyme activity in the membrane for most proteins.

Animals↗
PubMed2000

Relating testosterone levels and free play social behavior in male and female preschool children.

This study assessed potential relationships between a series of behavioral measures seen in the interactions of preschool children with their peers (particularly aggressive behavior) and testosterone levels. 28 boys and 20 girls of preschool age were videotaped in free play interactions. Their behavior was then evaluated with particular emphasis on aggression and affiliation in play and social interactions. Testosterone levels were measured using radioimmunoassay in saliva samples. Correlation analysis revealed a positive relationship in boys between testosterone and giving and receiving aggression in the context of 'social interactions' (serious aggression), but not in the context of play (playful aggresstion). Testosterone can be a useful biological marker for serious aggression (and behavioral patterns reflecting different levels of sociability) in preschool boys.

Aggression↗
PubMed2000

Dietary fats influence consumption and metabolic measures in male and female laboratory mice.

Juvenile and adult male and female Swiss mice in metabolism cages were fed one of four specially-formulated, pelleted diets containing respectively 8% saturated vegetable fat, 8% soya oil, 8% olive oil and 2% soya oil. The identities of the diets were hidden from the experimenter. Subjects were individually housed in metabolism cages and their consumption of food, growth and eliminative activities were measured. Clearly, these non-isocaloric diets differed in palatability, producing complex effects on growth as well as metabolic measures. Many indices were influenced by age, sex, and the duration of dietary exposure. Interactions between factors were common. Dietary fats appear to have subtle effects on the physiology and behaviour of rodents and may account for some differences between studies.

Aging↗
PubMed1999

Effect of predatory stress on sucrose intake and behavior on the plus-maze in male mice.

In this study, the effect of the exposure of male mice to sensory stimuli from rats was assessed on both sucrose intake and the elevated plus-maze tests. CDl male mice were trained in the sucrose intake task (the prestress phase) and, subsequently, distributed into two groups. The stressed group was accommodated in the same room as rats and the control group with mice (the stress phase). After being transferred, animals were tested on sucrose intake and the plus-maze (acute tests) and retested three times a week for sucrose intake and once on plus-maze on the last day (chronic tests). After acute exposure to the predator, the only difference between stressed and control animals was a higher number of fecal boli left on the plus-maze by the former. During the chronic phase, stressed animals showed a lower level of sucrose intake and higher level of anxiety than controls. In conclusion, this study shows that chronic exposure of male mice to stimuli from rats reduces the sensitivity to the rewarding properties of sucrose and prevents the habituation to the plus-maze observed in controls. Thus, this study suggests that exposure of mice to sensory stimuli from rats may provide an animal model of stress, and that these species should not be routinely housed together.

Analysis of Variance↗
PubMed1999

Effects of chronic mild stress (CMS) and imipramine administration, on spleen mononuclear cell proliferative response, serum corticosterone level and brain norepinephrine content in male mice.

There is increasing evidence that stress and emotional reactions produce changes in various immune processes. These changes may be due to alterations of the stress responses endocrine and for autonomic mediating mechanisms. In order to study such effects, the impact of chronic mild stress (CMS) application, and of subsequent imipramine administration were studied on the spleen mononuclear cell proliferative response period. OFI strain male mice were subjected to 4 or 7 weeks of CMS. The effects of these treatments on serum corticosterone levels and hypothalamic and hippocampal norepinephrine (NE) contents were also assessed. Subjects submitted to CMS had a higher spleen mononuclear cell proliferative response after either treatment duration. Imipramine treatment diminished this response enhancement in CMS exposed animals, but did not alter the proliferative responses of control subjects. Serum corticosterone levels, as well as hypothalamic and hippocampal nonrepinephrine contents did not significantly vary between groups. Taken together, these results suggest that CMSs effects on immune reactivity are not related to serum glucocorticoids or NE changes in these locations associated with the hypothalamic-pituitary- adrenocortical (HPA) axis.

Adrenergic Uptake Inhibitors↗
PubMed1999

A re-evaluation of social defeat as an animal model of depression.

Social defeat by aggressive Tryon Maze Dull (TMD) rats, resulting in loss of rank of a previously dominant rat, has recently been advanced as a model of loss of self-esteem in humans. Since low self-esteem is a major symptom of depression, a further claim has been made that loss of rank can be used as a model of depression. In support of this claim, it has been suggested that loss of rank can be reversed by the antidepressant imipramine. However, antidepressant treatment has not yet been shown to reverse the effects of defeat for more than a single test session. Consequently, the present study was designed to more fully assess the effects of antidepressant treatment on the behaviour of defeated animals. Six pairs of male Lister Hooded (LH) rats were observed biweekly for 30 min at the onset of the dark phase of the light-dark cycle. In five of the six pairs, a stable social hierarchy (assessed by the observation of aggressive behaviours such as attacks and pushes, and submissive behaviours such as submissive posture) was established over a period of 10 weeks. The dominant animals of these five pairs were defeated once a week, in the home cage, by a singly housed male TMD for a period of 15 min. After 5 weeks of defeat by TMD, all five of the dominant animals showed an effect of defeat on behaviours relevant to status, although a reversal in status within the LH pairs was apparent in only one case. All defeated animals, regardless of whether or not defeat affected status, received daily injections of imipramine (5 mg/kg) for 5 weeks. Imipramine markedly worsened behaviours relevant to status in the treated animals. Indeed, animals treated with imipramine were more likely to lose encounters with their cage-mates. Consequently, the results cast doubt on the validity of social defeat as a model of depression, at least when the effects of defeat are assessed in terms of social status.

Aggression↗
PubMed1998

Changes in the neuronal membranes of mice related to steroid hormone influences.

Changes in the biochemical composition of synaptosomal plasma membranes (SPM) isolated from mouse brains have been measured. The protein, phospholipid, and cholesterol contents all increased over the first 30 days of postnatal life, with the cholesterol to phospholipid molar ratio (one of the major determinants of lipid fluidity) also increasing in direct relation to the decrease in lipid fluidity. The fatty acid composition of SPM also changes with the increase in 18:0, and the decrease in 18:2, 18:3, and 22:4, in keeping with the increase in membrane order. Steroid hormones alter lipid fluidity to a greater degree in fluid membranes, indicating that the nongenomic effects of steroids will be most prevalent in membranes during the early prenatal period and for the first days following birth. The potential effects of xenobiotics on membrane fluidity are also discussed.

Animals↗
PubMed1996

Preferential occupation of mineralocorticoid receptors by corticosterone enhances glutamate-induced burst firing in rat midbrain dopaminergic neurons.

Sensitisation to the behavioural effects of amphetamine, a phenomenon which appears to involve the potentiation of excitatory amino acid (EAA)-mediated transmission at the level of dopaminergic (DA) neurons in the ventral tegmental area (the A10 cell group), is known to be affected by corticosteroid manipulations. Since there is evidence that corticosteroid manipulations can also influence unpotentiated EAA-mediated transmission elsewhere in the brain, the possibility was examined that the same may be true for midbrain DA neurons. The effect of iontophoretically administered glutamate on the activity of A10 DA neurons was investigated in adrenalectomised animals given a low dose of corticosterone intravenously (equivalent to 13.4 micrograms/100 ml plasma - likely to preferentially occupy the mineralocorticoid subtype of corticosteroid receptor) at least 45 min (median 132.5) prior to recording. Cells from these animals were compared to those from adrenalectomised and sham operated animals administered saline. Adrenalectomy significantly reduced the firing rate of A10 cells, and this effect was reversed by corticosterone replacement. Adrenalectomy did not affect basal burst firing. However, in those cells which could be classified as "bursting' under basal conditions, cells from animals administered corticosterone showed enhanced glutamate-induced bursting relative to the other two groups. The degree of enhancement was strictly determined by the basal bursting level of the cell. Since the distinction between "bursting' and "non-bursting' DA neurons is probably not related to differences at the level of the EAA receptor/effector mediating bursting, it is argued that corticosterone's facilitation of glutamate-induced bursting is not produced at this level, but rather at the level of an intrinsic membrane property which modulates bursting.

Adrenalectomy↗
PubMed1996

Long-term chronic treatment with stanozolol lacks significant effects on aggression and activity in young and adult male laboratory mice.

1. Repeated doses of the anabolic-androgenic steroid stanozolol were assessed for their effects on agonistic behavior, motor activity, and body weight in both young and adult male laboratory mice. 2. Stanozolol significantly increased weight gain in young, but not older subjects, especially at the highest doses. 3. There were, however, no significant differences in motor activity or in ethologically assessed social behavior (including aggression) in young or adult mice.

Age Factors↗
PubMed1995

Attenuation of sucrose consumption in mice by chronic mild stress and its restoration by imipramine.

Chronic exposure to mild unpredictable stressors (CMS) has previously been found to reduce the consumption of palatable, sweet solutions in rats. In the present study, the utility of this procedure was assessed in mice. Male AP mice subjected to CMS showed reduced consumption of a 2% or 4% sucrose solution. This effect was reversed by chronic (3 weeks) treatment with the tricyclic antidepressant imipramine (20 mg/kg per day). These results extend previous reports of a generalized decrease in sensitivity to reward (anhedonia) in rats caused by CMS and the efficacy of antidepressant treatment in this paradigm. Chronic unpredictable mild stress in mice appears to provide a realistic animal model of depression.

Analysis of Variance↗
PubMed1993

Aggression in female mice: contrasting effects of amiflamine (FLA 336), a selective and reversible MAO-type A inhibitor.

The effects of FLA 336 on the attack by resident groups of female mice on strange female intruders were assessed. This MAO-type A inhibitor clearly suppressed attack in treated subjects without producing major alterations in other activities but there was no clear dose-response relationship. The substance also increased attack on treated animals, an effect largely mediated via changes in the odor characteristics of the urine. The data emphasize the need for appropriate controls in studies with psychoactive compounds to distinguish direct (CNS-mediated) from indirect (mediated via changed signalling or perception) actions.

Aggression↗
PubMed1993

Effects of two selective dopaminergic antagonists on ethologically-assessed encounters in male mice.

1. Although it is accepted that dopaminergic antagonists suppress aggressive behaviour, the drugs used have been relatively non-selective or specific to the D2 receptor. 2. The selective D1 antagonist, SCH 23390, makes it possible to evaluate the impact of this receptor on aggressive behaviour. 3. The effects of SCH 23390 and Spiperone (a D2 antagonist) on the aggressive behaviour of mice were assessed employing a "standard opponent" test. 4. Both drugs markedly decreased aggressive behaviour whilst increasing immobility. However, whilst SCH 23390 increased immobility to a small extent, Spiperone, produced a general decline in active behaviours. 5. It appears that the D1 receptor inhibition of aggression is the more specific.

Aggression↗
PubMed1993

Diversity of animal models of aggression: their impact on the putative alcohol/aggression link.

Many attempts have been made to "model" the putative link between alcohol and "aggression" using a variety of situations employing a wide range of animal species. In general, these attempts have proved somewhat disappointing. One reason for this appears to be the fact that the different "aggression" tests tap varied mixtures of offensive, defensive and predatory motivations (i.e., they are not homogenous). Indeed, one can make the claim that the majority of examples of "aggression" associated with alcohol-ingesting humans are inappropriate (nonadaptive) responses whereas many animal models tap adaptive territorial or socially competitive actions. A further problem is that alcohol has very wide-ranging effects on neurophysiology and endocrine functioning. Recent evidence from studies on infra-human animals and clinical situations suggests that some of alcohol's effects on social conflict are expressed by actions in signaling and perception rather than motivation. This aspect is briefly examined in some studies with laboratory mice.

Aggression↗
PubMed1992

Clozapine: strong antiaggressive effects with minimal motor impairment.

Clinical studies have shown clozapine to be effective in the treatment of schizophrenia and associated with an extremely low incidence of extrapiramidal side effects. Diverse studies indicate that clozapine is an atypical neuroleptic with a preferential activity on the mesolimbic structures and a lower affinity for striatal D2 receptors than the classical antipsychotics. The purpose of this study was to assess the behavioral properties of clozapine, especially its effects on aggressive and motor behaviors. Individually housed male mice of the OF1 strain were exposed to anosmic "standard opponents" 30 minutes after the last drug administration. One category of animals received a single IP dose of the compound (0.2, 0.5, 1 or 1.5 mg/kg). Another category received daily doses (0.5, 1 or 1.5 mg/kg) for 21 days. Encounters were videotaped and behavior evaluated using an ethologically based analysis. Clozapine, in the acute treatment condition, produced a significant decrease in "attack" and "threat" behaviors without "immobility" being significantly increased. These results suggest a rather specific antiaggressive action of the compound with little motor impairment. In the chronic administration, no significant change in aggressive behavior was observed which may be attributed to the development of some degree of tolerance.

Aggression↗