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…

Effects of cigarette smoking on time estimation

Editorial: Mindfulness y Psicoterapia 10 años después (2006-2016)

espanolEditorial del monografico Mindfulness y Psicoterapia 10 anos despues (2006-2016) EnglishFrom the Editor: Mindfulness and Psycotherapy 10 years later (2006-2016)

Effects of competition and its outcome on serum testosterone, cortisol and prolactin.

In various species, competitive encounters influence hormonal responses in a different way depending on their outcome, victory or defeat. This study aimed to investigate the effects of sports competition and its outcome on hormonal response, comparing it with those displayed in situations involving non-effort and non-competitive effort. To this end, serum testosterone (T), cortisol (C) and prolactin (PRL) were measured in 26 judoists who participated in three sessions (control, judo fight and ergometry). The relationship between hormonal changes and psychological variables before and after the fight were also analysed. Our results showed a hormonal response to competition, which was especia…

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…

Testosterone and cortisol responses to competitive fighting in human males: A pilot study

Departamento de Psicologia Fisiologica (A.S., V.S., F.S.) and Laboratorio de MedicinaNuclear e Isotopos (L.L.), Hospital Clinico Universitario, Universitat de Valencia, Valencia,SpainSerum testosterone and cortisol levels were measured by radioimmunoassay in 14young male judo competitors, in samples taken 10 minutes before and 45 minutes aftertwo different pr(Redures. The first involved physical exercise and the second competi-tive fighting. Both procedures were of 5 minutes duration and sessions took plate atthe same time (between 10:00 \.M. and 12:00 P.M. liR-al lime) but on different days.Comparing the two situations over all subjects revealed that testosterone increasedafter exercise an…

Gender differences in the effects of haloperidol on avoidance conditioning in mice

Abstract Gender differences in the effects of haloperidol (0.07S mg/kg per day for 5 days) on avoidance conditioning were evaluated. We also studied performance of the subjects free of the drug and the acute effects of haloperidol in animals trained without drug 48 h after the last haloperidol administration. Latencies of escape and avoidance responses, number of nonresponses, escapes, avoidances, crossings during the adaptation period, crossings during intertrial intervals, and total crossings per minute were analyzed. This dosage impaired conditioning of the male animals but did not attain the same effects on females. Haloperidol did not deteriorate performance of the task when it had bee…

Interaction of morphine and haloperidol on agonistic and motor behaviors of male mice.

To further clarify the interaction between opioid and dopaminergic systems, the effects of simultaneous administration of morphine hydrochloride (1.25 or 2.5 mg/kg) and haloperidol (0.1 mg/kg) on aggressive behavior of male mice were explored. Isolated male mice (experimental animals) were confronted in a neutral area with anosmic, group-housed consepecifics (standard opponents) 30 min after injection of both compounds, and aggression was evaluated by estimation of times allocated to 11 different behavioral categories. In the first experiment (which functioned as a pilot study), the two doses of morphine were explored. In the second one, incorporating a more complete experimental design, on…

Sex differences in the effects of neuroleptics on escape-avoidance behavior in mice: a review.

Abstract The literature of the effects of dopamine antagonists on escape-avoidance, focusing on data obtained in our laboratory with male and female mice, is reviewed. The acute administration of haloperidol, raclopride, clozapine, and SCH 23390 impaired escape-avoidance behavior more in males than in females, and the subchronic administration of haloperidol had a similar effect. This appeared to be a reliable phenomenon, because it was observed in both kinds of administration, in two mouse strains, and with several drugs and doses. The observed results were dose dependent, although the dose–effect relationship was not the same in all drugs. The sex differences in escape avoidance did not s…

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…

Time estimation in minimally abstinent smokers

A new apparatus for the study of avoidance conditioning in fishes

An apparatus for the study of avoidance conditioning in fishes is described. The chamber is cylindrical in shape, with shocking electrodes placed above and below the animals, and response is defined as swimming a predetermined distance in either direction along a circumferential path. This apparatus has several advantages over the conventional shuttlebox: (1)There is little constraint on the direction of swimming; (2) the magnitude of response (swimming distance) required for avoidance can easily be varied over a wide range; and (3) variation in the effectiveness of shock with the position of the animal relative to the position of the electrodes is minimized. Some sample data obtained in a …

Lack of effects of anabolic-androgenic steroids on locomotor activity in intact male mice.

Anabolic-androgenic steroid abusers have reported hyperactivity euphoria, and decreased fatigue, among other behavioral effects. It has been suggested that the effects of these substances on the central nervous system are similar to those of psychostimulants; however, the influence of steroids on general locomotor activity in laboratory animals is not well understood, especially how noncastrated male rodents are affected. In this study, spontaneous locomotor activity displayed by gonadally intact male mice submitted to several experimental conditions was analyzed. Different housing conditions (individual or cohabiting with a female), diverse steroids (testosterone propionate, nandrolone de…

Predicting how equipotent doses of chlorpromazine, haloperidol, sulpiride, raclopride and clozapine reduce locomotor activity in mice

Distinguishing the specific effects of neuroleptics on one particular behaviour from its non-specific effects on motility is not easy. In this study, the effects of five neuroleptics on spontaneous motor activity were compared and the ED(50) values of these drugs to impair activity were calculated. Male and female mice were evaluated in an actimeter or in a shuttle-box used as an open field after the administration of chlorpromazine (0.4, 1.2, 3.6 mg/kg), haloperidol (0.1, 0.3, 0.9 mg/kg), raclopride (0.1, 0.3, 0.9 mg/kg), sulpiride (10, 30, 90 mg/kg) and clozapine (0.4, 1.2, 3.6 mg/kg), and two automatic and two observational activity measures were obtained. A very high correlation between…

Acute and chronic effects of clomipramine on isolation-induced aggression in male mice

The behavioral effects of clomipramine were studied on an ethopharmacological model of aggression. A range of low doses (similar to those used in clinical practice: 1.5, 3, and 6 mg/kg) and a higher dose (24 mg/kg—more usual in animal experimentation) were administered to isolated male mice that confronted anosmic opponents in a neutral arena. Encounters were staged 30 min after acute treatment and either 30 min or 24 h after the last drug administration in the chronic (21-day) treatment. Significant behavioral effects were observed predominantly with the highest dose. Acute and chronic effects were similar in the sense that both decreased aggressive behavior and produced some impairment of…

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…

Dose-dependent impairing effects of morphine on avoidance acquisition and performance in male mice.

The effects of morphine (6.3, 12.6, and 25.2 mg/kg) on active avoidance behavior of BALB/C mice are explored in three acquisition sessions and in two subsequent performance sessions. Morphine-treated animals showed an increase in avoidance acquisition with respect to control group without differences in performance. However, a dramatical, concomitant rise in the locomotor activity of the animals (increase in the number of crossings during the intertrial intervals) prompted us to transform the data employing a formula with which a measure of actual learning was obtained. Applying this formula, we have observed that morphine administration impairs, dose-dependently, acquisition and performanc…

Effects of chronic treatment with testosterone propionate on aggression and hormonal levels in intact male mice.

Effects of testosterone propionate, an anabolic-androgenic steroid (AAS), on aggression in gonadally intact male mice were examined. Animals were given weekly injections of 3.75, 7.5, 15, and 30 mg/kg of drug or sesame oil for 10 weeks. During the last 3 weeks, behavioral tests were conducted and at the end of the experiment, body, liver and testes weight and hormonal data were collected. The treatment had minimal behavioral and endocrine effects. It resulted in shorter latencies of 'threat' only in the last agonistic encounter, increases in testosterone levels and decreases in testes weight in a non-linear dose-dependant way. The action of treatment was different on threat and attack, the …

Fostering Self-Compassion and Loving-Kindness in Patients With Borderline Personality Disorder: A Randomized Pilot Study

The aim of this randomized pilot study is to investigate the effects of a short training programme in loving-kindness and compassion meditation (LKM/CM) in patients with borderline personality disorder. Patients were allocated to LKM/CM or mindfulness continuation training (control group). Patients in the LKM/CM group showed greater changes in Acceptance compared with the control group. Remarkable changes in borderline symptomatology, self-criticism and self-kindness were also observed in the LKM/CM group. Mechanistic explanations and therapeutic implications of the findings are discussed. Highlights: Three weeks of loving-kindness and compassion meditations increased acceptance of the pres…

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…

Dose Dependency of Sex Differences in the Effects of Repeated Haloperidol Administration in Avoidance Conditioning in Mice

Sex differences in the effects of haloperidol in active avoidance conditioning in mice have previously been found in various studies carried out in our laboratory. Males were more affected than females by the disruptive effects of this neuroleptic. The work described here broadens the study of these sex differences to higher doses of haloperidol (0.1 and 0.2 mg/kg) using a repeated administration schedule (5 days). The results did not show sex differences in the deteriorating effects of this dopamine antagonist in the escape-avoidance response, but a tendency in the number of nonresponses was observed in the same direction as former results: male animals were more sensitive than females to …

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…

Morphine potentiates the impairing effects of neuroleptics on two-way active conditioned avoidance response in male mice

The dopaminergic and opioid systems have effects on the conditioned avoidance response (CAR), although the possible interaction between these systems on this behaviour has not been studied. The effects of morphine (12.6 mg/kg), haloperidol (0.075 mg/kg), sulpiride (20 mg/kg) and risperidone (0.1 mg/kg) alone as well as morphine combined with these dopamine (DA) antagonists on the acquisition and performance of the CAR were explored in mice. Morphine increased avoidances but this seemed secondary to a rise in activity levels. All DA antagonists impaired CAR in the acquisition phase but only haloperidol disrupted performance. The combination of morphine plus neuroleptics impaired acquisition …

The GABAergic effect of low doses of lorazepam on social behavior

The aim of this work was to test the antiaggressive effects of lorazepam and to determine whether these effects were mediated by benzodiazepine receptors. In a first experiment, male mice were injected with lorazepam in a range of low doses (0.05, 0.1, 0.2, and 0.6 mg/kg) or saline solution. In a second experiment, 1 mg/kg of Ro 15-1788, a benzodiazepine receptor antagonist, and a saline solution were injected before the behavioral test. Results showed that 0.6 mg/kg of lorazepam was the only dose that decreased the total duration of threat ( P < .01) and social investigation ( P < .05) and that 1 mg/kg of Ro 15-1788 had no effects. In the third experiment, animals received two injec- tions…

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…

Apparent vs real effects of scopolamine on the learning of an active avoidance task.

The effects of scopolamine hydrobromide (0.5 and 2 mg/ kg) administered intraperitoneally to Balb/c male mice before or after training in active avoidance were explored in four training sessions and in a subsequent test session, free of drug. Animals given scopolamine prior to training performed better than controls, an effect that was reversed in the session free of drug. However, a deeper analysis of the data permits us to interpret this increment in the number of avoidance responses as a consequence of the increase in activity produced by the drug and not as learning. In the animals injected with scopolamine after sessions no effects were observed. In conclusion, the results of the prese…

Gender differences in escape-avoidance behavior of mice after haloperidol administration.

Gender differences in the disruptive effects of haloperidol on some reinforced behaviors have been observed in different species. However, the inhibitory action of haloperidol on the acquisition and performance of escape-avoidance behavior has only been investigated in male subjects. The present experiment was designed to investigate possible gender differences in the effects of haloperidol on the initial phase of an escape-avoidance learning task. Male and female mice of the OF1 strain were given a single training session in a shuttle-box. Thirty minutes prior to the behavioral test, mice were injected IP with haloperidol (0.25 mg/kg) or physiological saline (10 ml/kg). Latencies of escape…

Effects of risperidone and SCH 23390 on isolation-induced aggression in male mice.

In this study, the antiaggressive effects of risperidone and SCH 23390 have been explored. Using the paradigm of isolation-induced aggression, 150 albino male mice of the OF1 strain were allocated to control and experimental groups which received three doses of risperidone (0.01, 0.05 and 0.1 mg/kg) or two doses of SCH 23390 (0.05 and 0.1 mg/kg). Only the highest doses of risperidone decreased threat and attack behaviours but all doses significantly impaired motor behaviour. SCH 23390 decreased attack with the two doses used and also produced significant increases in immobility. Although both antipsychotics are antiaggressive, this action seems to be more specific in the case of risperidone…

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…

Development of tolerance to the antiaggressive effects of morphine

Many reports have demonstrated that there is a development of tolerance to many effects produced by morphine. This study was conducted with the aim of determining whether the antiaggressive actions of morphine develop tolerance after chronic administration. Acute morphine administration produced antiaggressive effects which disappeared after chronic (7 days) treatment in isolated mice. An increase in non-social exploration was observed, representing morphine-induced hyperactivity, after acute treatment, which was not present after chronic administration. In conclusion, there is a development of tolerance to the antiaggressive and motor effects of morphine. Language: en

Successful intermale aggression and conditioned place preference in mice

A. SALVADOR AND V. M. SIMON. Successful intermale aggression and conditioned place preference in mice. PHYSIOL BEHAV 58(2) 323-328, 1995.--This study assessed the reinforcing properties of successful intermale agonistic encounters between OFI male mice using the conditioned place preference paradigm. A three compartment apparatus was used and the procedure consisted of three phases: preconditioning (3 days), conditioning (8 days) and postconditioning (3 tests). Individually housed male mice were allocated to two groups. The aggression group confronted docile opponents in the preconditioning "less-preferred" compartment and were left alone in the "preferred" one. The control group was left a…

Behavioral changes over several successful agonistic encounters between male mice: Effects of type of “standard opponent”

This study assessed whether two types of non-aggressive “standard opponents” (“intact” and “anosmic” group-housed males) produced similar behavioral changes in isolated OF1 male mice given several experiences of victory. Experimental groups confronted either intact or anosmic opponents every two days until they had completed four encounters. The behavioral changes were recorded using a detailed ethologically inspired analysis. These changes were clearly different depending on the opponent type. When intact opponents were used, experimental subjects increased the time spent in digging, non-social exploration, explore from a distance, and attack over encounters, but showed decreased time spen…

Antiaggressive and motor effects of haloperidol show different temporal patterns in the development of tolerance.

Abstract The study of the temporal course of tolerance development was used as a means to separate different aspects of the action of haloperidol on social behavior. Agonistic behavior was studied in isolated male mice that confronted standard opponents (anosmic and grouped conspecifics) in a neutral area. The aggressive and motor behaviors of the experimental animals were evaluated 30 min or 24 h either after a single injection of haloperidol (0.4 mg/kg) or following the last of a series of 15 or 30 injections. When animals were evaluated 30 min after the haloperidol injection, no tolerance to the antiaggressive effects was evident. The action on immobility, on the contrary, showed a clear…

Changes in the structure of the agonistic behavior of mice produced by D-amphetamine.

The effects of three acute doses of D-amphetamine (0.25, 1.5 and 3 mg/kg) were studied in a model of isolation-induced aggression in male mice. An ethopharmacological analysis of the encounters was carried out, which studied the frequency, total and mean duration of different behavioral categories, including the temporal distribution of attacks and the duration of inter-attack intervals. The results show a reduction in the total and mean duration of the Attack category and an increase in motor activity manifested by longer durations, both total and mean, of Non Social Exploration and shorter Immobility. The temporal analysis of Attack revealed an increase in the number of very short (< 15 s…