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Biomedical subjects

P F Brain

Publications and source records attributed to P F Brain.

At least 37 records · Page 2Linked to original sources
PubMed1992

Effects of exposure of pregnant mice to chlordiazepoxide (CDP) on the development and ultrasound production of their offspring.

1. The effects were studied of injecting pregnant Alderley Park mice with the benzodiazepine agonist chlordiazepoxide (CDP) at doses of 10 and 30 mg/kg during the last 9-10 days of gestation on the early behaviour and development of their offspring. 2. All neonates were fostered to non-treated lactating dams to eliminate maternally-mediated effects. 3. Early development and responses to anxiety-related situations were studied by recording body growth, righting reflex, rooting behaviour, cliff avoidance reflex and ultrasonic "distress" calling. 4. Drug treatment: (a) retarded postnatal body growth; (b) delayed the righting and cliff avoidance reflexes; (c) augmented rooting behaviour and (d) produced an overall increase in ultrasonic calling (but with the higher dose decreasing emission on days 1-2). 5. Exposure to CDP during foetal life retards motor development and physical maturation; produces a sedative/anxiolytic action (especially at high doses) and may modify the sensitivity of GABA-BZP receptor complex to endogenous receptor ligands.

Analysis of Variance↗
PubMed1992

Hormonal and neurochemical correlates of various forms of animal "aggression".

The majority of studies attempting to evaluate the roles of hormones and neurochemicals in "aggression" concern laboratory rodents, notably rats and mice, with fewer investigations on infrahuman primates. Studies suggest that situations used to assess aggression (e.g., social conflict tests, parental attack, predatory behavior, use of unavoidable electroshock) actually tap a diverse range of motivations whose functions include offense, defense and predation. It is also apparent that ethoexperimental techniques, i.e., those applying ethological methodologies and concepts to laboratory situations, have advantages in assessing the direct and indirect consequences of chemical treatments. In this review, the impacts of hormonal manipulation (by surgery and/or application) and varying neurotransmitters (studied in terms of regional changes and as consequences of drug treatments) on a variety of forms of behavior are assessed. Different tests do show varying responses to common treatments, confirming the heterogeneity of the available paradigms. A brief discussion is provided of which tests are likely to prove most relevant to clinical studies.

Aggression↗
PubMed1991

Sulpiride has an antiaggressive effect in mice without markedly depressing motor activity.

The atypical neuroleptic, sulpiride is a selective D2 antagonist, having a preferential action on mesolimbic regions. The effects of acute and chronic treatment with sulpiride on aggressive behaviour in male mice were studied using an ethologically based analysis. It was hypothesized that sulpiride would diminish "threat" and "attack" but would not produce marked "immobility", because of the mesolimbic effect referred to above. Isolated albino male mice (experimental animals) were confronted by "standard opponents". Acutely-treated experimental animals received an intraperitoneal injection of sulpiride (20, 50 or 100 mg/kg) 30 min before testing. Chronically-treated animals received sulpiride (10, 20 or 50 mg/kg) once a day for 7 or 14 consecutive days. Acute treatment with sulpiride had an obvious antiaggressive effect, with significantly decreased time devoted to "attack" and "threat" behaviour. Although time spent in "immobility" was modestly increased, the time devoted to other motor behaviour was also increased. Chronic treatment for 1 or 2 weeks did not change any behavioural category, except "immobility". The antiaggressive action of acutely administered sulpiride is interpreted as a relatively specific dopaminergic antagonist effect and not as merely a non-specific correlate of its disruptive action on motor behaviour. The possible anxiolytic action of sulpiride is also discussed.

Aggression↗
PubMed1991

Effects of prenatal exposure to benzodiazepine-related drugs on early development and adult social behaviour in Swiss mice--I. Agonists.

1. The present experiment examined, using a battery of tests, the effects of in utero exposure to the benzodiazepine agonists chlordiazepoxide and midazolam upon the early development and adult behaviour of offspring of Swiss mice. 2. Early development was generally retarded as a result of treatment. 3. Effects on adult social behaviour examined using the resident-intruder paradigm by determining the time spent in broad behavioural categories, showed marginal effects due to chlordiazepoxide and more striking actions due to midazolam treatments. Generally the treatments produced changes suggestive of an increase and a decrease in anxiety in males and females respectively.

Animals↗
PubMed1991

Effects of prenatal exposure to benzodiazepine-related drugs on early development and adult social behaviour in Swiss mice--II. Antagonists.

1. The present experiment examined, using a battery of tests, the effects of in utero exposure of Swiss mice to the benzodiazepine antagonists Ro 15-1788 and CGS 8216 upon early development and adult behaviour. 2. Early development was facilitated by treatment of Ro 15-1788. CGS 8216 suppressed during later development. Effects on the righting reflex were seen on different postnatal days following exposure to different treatments. The other factors studied remained unaffected. 3. Effects on adult social behaviour were examined using the resident-intruder paradigm, by determining the time allocated to broad behavioural categories. Increases in attack and threat in male offspring of dams treated with Ro 15-1788 and CGS 8216 were found. Female offspring differed from controls in digging and defensive/submissive behaviour.

Animals↗
PubMed1991

Effects of prenatal exposure to benzodiazepine-related drugs on early development and adult social behaviour in Swiss mice--III. Inverse agonists.

1. The present experiment examined, using a battery of tests, the effects of in utero exposure to the benzodiazepine inverse agonists DMCM and FG 7142 upon the early development and adult behaviour of Swiss Mice. 2. Early development was respectively retarded and augmented by treatments with the higher and lower doses of DMCM. FG 7142 suppressed later development. DMCM retarded righting reflex on certain days. FG 7142 had a significant, biphasic effect on eye opening. 3. Adult social behaviour was examined using the resident-intruder paradigm, by determining the time spent in broad behavioural categories. Male offspring of dams treated with DMCM showed increased threat. FG 7142 had no significant effects.

Animals↗
PubMed1991

The effects of 5-HT receptor ligands on ultrasonic calling in mouse pups.

The influence of a range of drugs acting at various 5-HT receptor sites on the ultrasonic calling of mouse pups was assessed. Calling was decreased by the novel anxiolytics buspirone, ipsapirone and gepirone, and by TFMPP, spiperone, ritanserin and GR 38032F. In contrast, 8-OH-DPAT, DOI and quipazine increased the rate of calling. These effects on ultrasonic calling were independent of sedative or thermoregulatory actions of these drugs. Present data provide further support for the view that ultrasonic calling can be used to assess novel compounds for possible anxiolytic or anxiogenic properties.

Animals↗
PubMed1991

Ethopharmacological studies on the effects of antihormones on rodent agonistic behavior with especial emphasis on progesterone.

The effects of a range of antiandrogens and antiestrogens on conflict behaviors in laboratory rats and mice are reassessed in the light of recent studies applying ethophamacological analyses (recording the full spectrum of behaviors) to such investigations. It is argued that any antihostility properties of the antiandrogen cyproterone acetate are largely a consequence of indirect actions on odor communication, whereas antiestrogens (e.g., tamoxifen and CI 680) seem to have more fundamental motivational effects in addition to communicatory actions. A detailed example of the approach is provided in which progesterone (which can be antiandrogenic) is given to rats paired in different ways. The type of pairing has a very substantial effect on the actions seen after treatment, and the ethopharmacological approach generates a better picture of antihormone effect than traditional psychopharmacological tests.

Agonistic Behavior↗
PubMed1990

Haloperidol does not antagonize the effects of stress on aggressive behaviour in mice.

The possibility that antipsychotic drugs antagonize the behavioural effects of stress on agonistic behaviour has been explored. Male mice of the OF.1 strain were subjected to the following treatments: 1) Immobilization stress (ten or twenty minutes in duration), 2) haloperidol (three doses) and 3) immobilization stress (ten minutes) plus haloperidol. Individually housed experimental animals confronted standard opponents (anosmic animals) in ten-minute encounters in a neutral cage. Encounters were videotaped and behaviour evaluated, assigning times allocated by subjects to eleven broad behavioural categories. The data show that stress markedly decreases attack behaviour, but haloperidol does not protect against the disruptive action of immobilization. On the contrary, stress and haloperidol produced additive effects further decreasing attack and increasing immobility.

Aggression↗
PubMed1990

Effects of 8-OH-DPAT and fluoxetine on activity and attack by female mice towards lactating intruders.

1. The impact of the serotoninergic receptor on the attack directed by female mice towards lactating intruders was assessed by studying the effects of 8-OH-DPAT (a serotoninergic agonist) and fluoxetine (an inhibitor of serotonin reuptake) on this paradigm at a range of doses and post-injection durations. 2. The specificity of these drug actions behaviour were examined by studying their effects on wheel running activity and performance in the open field. Non-sedative doses of 200 and 250 micrograms/kg of 8-OH-DPAT reduced attack by resident females on lactating intruders. 3. Higher doses (12-16 mg/kg) of fluoxetine reduced activity measures whereas lower non-sedative doses (up to 8 mg/kg) were without action on this aggression paradigm. 4. Additional studies with specific serotoninergic drugs are needed to clarify the role of this transmitter in attack by female mice on lactating intruders.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

The inhibitory effects of fluprazine on parental aggression in female mice are dependent upon intruder sex.

Lactating resident mice respond differently to male and female intruder conspecifics, showing defensive attack towards the former and offensive attack towards the latter. The effects of fluprazine (1-5 mg/kg) on this differential response pattern have been assessed. Although fluprazine increased the latencies of attack on male intruders, a very much more potent inhibitory effect was observed on attacks directed towards female intruders. Fluprazine also modestly reduced social investigation of female intruders and increased nest-oriented behaviour irrespective of the intruder's sex. As the pattern of attack on intruders, exploration, fear responses and maintenance behaviour all remained largely intact under drug treatment, it seems unlikely that the drug's inhibitory action on attack involves fear potentiation and/or olfactory impairment. It is suggested that the greater sensitivity of offensive attack to the inhibitory actions of fluprazine may reflect the relative degree of threat to resident parental investment posed by male and female conspecific intruders.

Aggression↗
PubMed1989

Suppressive effects of dehydroepiandrosterone and 3-beta-methylandrost-5-en-17-one on attack towards lactating female intruders by castrated male mice.

Three experiments were performed. In Experiment I, triads of adult castrated male mice were chronically administered with either oil-vehicle or 80 micrograms/day of dehydroepiandrosterone (D) or 3-beta-methylandrost-5-en-17-one (D-CH3). They were subsequently tested for their attack on a lactating intruder female introduced for 15 min in their home-cage, 2 hr after their last injection. Both D and D-CH3 significantly reduced male aggressive responses (cf. oil-injected category). In Experiment II the effects of D-CH3 dosed at 20, 40 or 80 micrograms/day were measured in the same testing situation. D-CH3 dose-dependently reduced the mice attack probability on lactating intruders with the highest dose being the most effective. Finally, to test in Experiment III that D-CH3 was not demonstrably androgenic, castrated males received daily injections of 20, 40 or 80 micrograms of this synthetic steroid for 4, 8, 16 or 32 days before tissue sampling. At all doses and whatever treatment duration, D-CH3 did not significantly increase the weights of the accessory sex organs.

Aggression↗
PubMed1989

A review of the history, actions, and legitimate uses of cocaine.

The history of cocaine is charted with specific reference to its usefulness as a medicine and local anesthetic. It is common knowledge that coca leaves were used as a panacea and local anesthetic throughout the history of the Incan Empire of Peru. In Europe, however, its medical usefulness was not fully recognized until Carl Koller used it to anesthetize the cornea of the eye. Over the next 20 years, cocaine became a popular medicine and tonic in Europe and America, where it was credited with curing a wide variety of diseases and illnesses. However, reports soon started to appear claiming that cocaine was a drug with a high social abuse potential and in America it seemed to underpin growing crime figures. As a result, cocaine was misclassified as a narcotic and its use was restricted to specific surgical procedures and medicinal preparations. Today, cocaine and its derivatives are still popular local anesthetics in operations of the ear, nose and throat and it is also used in a preparation given to alleviate the pain (physical and mental) of terminal diseases. Although cocaine has a high public profile as a drug of addictive potential, this drug has also had a long and distinguished history as a medicine and local anesthetic. The legitimate uses of cocaine exacerbate the problems of controlling this substance of abuse and should provide a stimulus for generating local anesthetics that lack addictive potential.

Americas↗
PubMed1988

Studies on effects of tamoxifen (ICI 46474) on agonistic encounters between pairs of intact mice.

The anti-estrogen tamoxifen (Tam), which has been shown to dramatically suppress offensive behavior in male rats without markedly influencing other aspects of the social encounter, was tested for its effectiveness in mice. TO strain albino mice were given control injections or 50 or 100 micrograms of Tam for 4 or 8 days. Subsequently, mice were tested in pairs (for a particular dose and treatment duration) in which both animals received Tam, one animal received Tam and one saline, or both animals received saline control injections. Ten-minute videotaped encounters were analyzed in terms of total times allocated to nonsocial investigation, social investigation, offense, defense, sexual activity/intense social investigation, and immobility. The lower dose given for the shorter duration produced less social investigation and more nonsocial investigation when Tam-treated subjects were paired together (cf. the Tam vs saline pairing). At all the other doses and durations, Tam reduced offense. Defense also changed in those pairings, but that activity seemed related to the amount of attack received. Tamoxifen had little influence on the weights of accessory sex glands. The data confirm that Tam is a potent suppressor of "androgen-dependent" aggression in male laboratory mice and provide further support for the aromatization hypothesis.

Aggression↗
PubMed1988

Different patterns of biting attack employed by lactating female mice (Mus domesticus) in encounters with male and female conspecific intruders.

Attacks by resident lactating female mice were examined in a variety of situations. Relatively few attack bites to vulnerable body regions were seen when pairs of unfamiliar lactating females fought, establishing social status prior to communal nesting. Sexually naive male and female intruders were equally prone to attack by lactating females, but patterns of bite attack generated by them were very different; males received the more damaging attacks. More signs of "fear" were seen in the lactating females' responses to male rather than female intruders. Varied motivations may underlie attacks by lactating females directed to conspecific intruders. Defensive patterns of biting by lactating females are more consistently directed towards males, intruders that are more likely to harm or destroy the litter. Although attacks by females rarely thwarted infanticide by male intruders, the behavior may acutely protect parental investment.

Aggression↗
PubMed1988

The potential of antiestrogens as centrally-acting antihostility agents: recent animal data.

Recent studies suggest that motivations for certain forms of masculine behavior including social aggression are mediated by central estrogen receptors. Two studies using antiestrogens in rodent species were performed. Intact male LH rats were given Tamoxifen or vehicle for 4 or 8 days. The three possible pairings were videotaped for 60 min. Intact male OF1 mice were given CI-680 or vehicle over 25 days. Similar pairings were carried out but some CI-680 or vehicle animals were paired with anosmic opponents. Encounters were videotaped for 10 min. In both experiments evidence was obtained that the antiestrogen markedly reduced time allocated to offense. Any variations in defense were a consequence of the level of attack to which animals were subjected. Neither compound greatly influenced the androgen-dependent sex accessory glands. Antiestrogens consequently have potential as antihostility agents in some forms of attack.

Aggression↗
PubMed1988

A reexamination of the hypoglycemia-aggression hypothesis in laboratory mice.

The suggestion of a clinical link between hypoglycemia and aggression has been recently encouraged by the work of Virkkunen and others. Modern techniques have impressively established a correlation between reactive hypoglycemia (low blood sugar levels engendered by stimulation of endogenous insulin secretion) and hostility as expressed in a variety of situations. It is not surprising that blood sugar levels influence behavior, as the brain is entirely dependent on glucose reaching it via the vascular system. In spite of this impressive link, there are remarkably few successful studies involving the effects of manipulating glucose levels on fighting in infrahuman animals. As there have been several methodological developments in this area it was thought appropriate to reinvestigate such phenomena in mice. The effects of injected bovine insulin and glucose were assessed using an ethopharmacological methodology applied to social encounters by isolated male Swiss mice with docile anosmic opponents. Although manipulation of blood glucose levels did not consistently change attack or defensive behavior, these treatments did modify aspects of the interactions.

Aggression↗