0000000000182272
AUTHOR
Paul F. Brain
Anti-anhedonic actions of the novel serotonergic agent flibanserin, a potential rapidly-acting antidepressant
Chronic exposure to mild unpredictable stress has previously been found to depress the consumption of palatable sweet solutions and to block the formation of conditioned place preferences; these effects are reversed by chronic treatment with tricyclic or atypical antidepressant drugs. The present study was designed to evaluate the antidepressant-like activity in this model of flibaserin (BIMT-17), a novel serotonergic agent with 5-HT1A receptor agonist and 5-HT2 receptor antagonist properties. Two experiments were conducted, using rats (experiment 1) and mice (experiment 2). In experiment 1, decreases in sucrose intake were seen in rats exposed to chronic mild stress, but the effect was unr…
Effects of two selective dopaminergic antagonists on ethologically-assessed encounters in male mice
Abstract 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 i…
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 sulpiri…
Effects of acute administration of nicotine and lobeline on agonistic encounters in male mice
The effects of acute administration of two nicotinic ligands, (-)-nicotine and (-)-lobeline were examined on isolation-induced aggression in mice. Individually housed male mice confronted anosmic “standard opponents” in a neutral arena 10 min after drug administration. Encounters were videotaped and evaluated using an ethologically based analysis facilitating estimation of time allocated to 11 broad behavioral categories. Nicotine did not have significant effects on threat or attack but significantly diminished time allocated to digging. The lowest dose of lobeline significantly diminished attack and induced a slight increase of immobility without significantly diminishing other behaviors w…
<Pheromones> and behaviour of rodents and primates
Abstract This paper reviews the concept of the ≪pheromone≫ as applied to behavioural studies on mammals with particular emphasis on rodents and primates. It is concluded that although the olfactory sense is very important in many representatives of these orders, the term pheromone is often used too uncritically in such species. Odours may certainly change behaviour but: (a) it is difficult to identify complex specific chemicals underlying such effects; (b) the response often depends on the nature and experiences of the recipient animal; and (c) many behaviours in such animals are modulated by a variety of sensory inputs. Perhaps ≪sociochemical communication≫ would be a better term to apply …
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…
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 consequ…
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…
Clozapine: Strong antiaggressive effects with minimal motor impairment
Abstract 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 sin…
Studies on the Effects of the Antiandrogen Cyproterone Acetate on Social Encounters Between Pairs of Male Mice
An attempt was made in two experiments to reinvestigate the effects of the antiandrogen cyproterone acetate (CA) on mouse social behavior in a variety of ethologically-assessed paired encounters. The data confirm that CA reduces offense (threat and attack) in animals when both subjects receive the material but that CA has no such action in other pairings. This suggests that CA's major suppressive effect on "hostility" is expressed in mice via a reduction in "attack-promoting" pheromone production. Indeed, there was evidence in the more chronic study that CA, could augment (via a central mechanism?) offense in subjects paired with docile anosmic opponents. Changes in defense were largely res…
An ethological analysis of the effects of diazepam and nitrazepam on the responses of female mice to anosmic males encountered in a novel arena
The effects of acutely administered benzodiazepines have largely been validated in male animals, in spite of the fact that the majority of anti-anxiety drugs are prescribed for female patients. A study was carried out assessing the potential of female mice in the testing of the anxiolytic properties of drugs. Three doses (0.5, 1.0 and 2.0mg/kg) of the benzodiazepines diazepam and nitrazepam were given to individually-housed female Swiss mice before dyadic encounters with anosmic, group-housed males. Videotape analysis of the encounters, using an ethopharmacological technique, revealed suppressive effects of diazepam (1.0 and 2.0mg/kg) and nitrazepam (all doses) on avoidance/flee, confirming…
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 mod…
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…
A specific anti-aggressive effect of repeatedly administered lobeline.
The effects of chronic treatments with nicotinic agonists on agonistic encounters have received little attention. The effects of repeated (for 10 days) SC administration of (-)-lobeline (9.3, 18.6 and 37.2 micromol/kg) and (-)-nicotine (0.93, 1.86 and 3.72 micromol/kg) were evaluated using the mouse isolation-induced aggression model. Individually housed OF1 male mice served as experimental animals and were confronted by 'standard opponents'. Each mouse was tested only once on the last day of the repeated drug treatment. Videotaped agonistic encounters were analysed estimating the times allocated to 11 behavioural categories. Repeated treatment with the highest dose of lobeline diminished a…
Correlating testosterone and fighting in male participants in judo contests
The role of hormones in human aggression is open to debate, but takes on a new urgency owing to the alarming abuse of androgenic anabolic steroids by some sports participants. In this study, video-taped behavior exhibited by 28 male competitors during a judo fight was assessed to analyze its relation to serum testosterone and cortisol levels measured before and after the bouts. A positive relation between testosterone and offensive behaviors was obtained in the sense that the greater the hormonal titer, the greater the number of threats, fights, and attacks. These findings coincide with the pattern of relationships found using observational scales. Conversely, cortisol also presented positi…
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 activ…