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J Mos

Publications and source records attributed to J Mos.

At least 55 records · Page 3Linked to original sources
PubMed1990

Ethopharmacology: a creative approach to identification and characterisation of novel psychotropics.

The present contribution describes the basic fundamentals of animal models in ethopharmacology. After defining the role of ethopharmacology in the development of animal models of relevant human diseases, this methodology is used to classify different categories of aggression. Furthermore, the behavioural aspects of agonistic (aggressive) modelling are outlined and the various models used to describe offensive and defensive behaviours, and some miscellaneous models are summarized. Finally, some remarks on the new class of psychoactive drugs, serenics, are given.

Animals↗
PubMed1990

Behavioural pharmacology of the serenic, eltoprazine.

In this paper the effects of serenics (eltoprazine and fluprazine) are described in several animal models for offensive agonistic, defensive agonistic and predatory behaviour. They are compared with the effects of a number of other putative anti-aggressive compounds or drugs used clinically in order to ameliorate aggressive behaviour of psychiatric patients. In isolation-induced offensive aggression in mice, eltoprazine has a marked and potent anti-aggressive activity, although numerous other psychoactive drugs also exert anti-aggressive effects. The behavioural specificity of this anti-aggressive profile was investigated using an ethologically derived animal model, social interaction in male mice. In this model, eltoprazine has a very specific anti-aggressive (serenic) profile, inhibiting aggression while social interaction and exploration are not decreased but even enhanced; inactivity, a measure for sedation, is not affected. Such a profile contrasts sharply with that of neuroleptics (chlorpromazine, haloperidol), psychostimulants (d-amphetamine) or benzodiazepines (chlordiazepoxide), which exert severe sedation (neuroleptics) or even aggression-enhancing effects (BDZ). After subchronic treatment no tolerance for the anti-aggressive effects of eltoprazine occurred. The specific anti-aggressive effects of eltoprazine were also found in rat models of offensive agonistic behaviour. In one such model - resident-intruder aggression - eltoprazine reduced offensive behaviour specifically, leaving social interactions and exploration intact, and did not induce sedation or other unwanted side-effects. The neuroleptic haloperidol was very sedative in this model, as was the 5-HT1A-agonist buspirone. Benzodiazepines (chlordiazepoxide) have a biphasic effect in this paradigm, enhancing offence at low doses and decreasing it at higher doses, due to muscle relaxation. In another offensive model, colony-aggression, in which a dominant and subordinate male in a colony are confronted with a male intruder, eltoprazine reduced offensive behaviour of both the dominant and the subordinate against the intruder. In contrast, chlordiazepoxide enhanced aggression, at least at lower doses, whereas alcohol had, up to very high doses, no effect on the offensive behaviour. In a brain-stimulation induced offensive model--hypothalamically-induced aggression in rats--eltoprazine specifically reduces offence. Locomotion, a measure for sedation, was either unaffected or even somewhat enhanced, indicating the absence of any sedatory activity of this serenic compound. In contrast, haloperidol heavily sedated animals, making them incapable of aggression.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Quantitative and comparative analyses of pro-aggressive actions of benzodiazepines in maternal aggression of rats.

The pro-aggressive effects of low doses of benzodiazepines on maternal aggression in rats were studied. Chlordiazepoxide, diazepam, oxazepam and alprazolam produced bell-shaped dose-response curves, with increased aggression at low doses. Only alprazolam significantly reduced aggression at higher doses. A comparison of the drug effects on different aggressive elements revealed that chlordiazepoxide and oxazepam increased the frequency of more elements of the aggressive repertoire than diazepam or alprazolam. Thus, although all benzodiazepine receptor agonists increased aggression, there were significant quantitative differences in their effects.

Aggression↗
PubMed1989

Serotonergic modulation of social interactions in isolated male mice.

Several serotonergic drugs were tested in isolation-induced aggressive behavior in male mice using ethological methodology. Eltoprazine, a mixed 5-HT1 agonist, reduced aggression but enhanced social interest and exploration. Several 5-HT1A agonists (8-OH-DPAT, ipsapirone, buspirone, 5-Me-ODMT) and a 5-HT uptake blocker (fluvoxamine) also reduced aggression. Although these drugs somewhat differentially affect aggressive behavior, the isolation-induced paradigm alone is not sensitive enough to successfully differentiate and screen the various serotonergic drugs with regard to their influence on social behavior in mice. It is argued that various animal paradigms in several species are necessary to describe specific effects of serotonergic drugs.

Aggression↗
PubMed1989

Brain 5-HT and inhibition of aggressive behavior in animals: 5-HIAA and receptor subtypes.

Evolutionary constant serotonin (5-HT) neuronal systems evolved along medial brain structures; yet, wide variations in functionality characterize serotonergic systems in mediating aggressive responses in species ranging from lobsters, ants, electric fish, and rodents to primates. So far, the attempts to correlate cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) levels with measures of aggression have revealed inverse, direct, or no correlations in different nonhuman primate species. It is difficult to harmonize the occasional correlations between CSF 5-HIAA and adaptive aggressive acts in nonhuman primates (a) with clinically diagnosed suicidal or impulsive individuals, and (b) with the biochemical, anatomical, and presumably functional differentiation of 5-HT pathways and receptor subtypes. Eltoprazine, a mixed 5-HT1A/B agonist, and meta-trifluoro-methylphenyl-piperazine HCl (TFMPP), a more selective 5-HT1B agonist, specifically decrease aggressive behavior in several animal species and situations in both sexes without detriment to other social, exploratory, or motoric activities. A definite role for 5-HT1A, 5-HT2, and 5-HT3 receptor subtypes in the mechanisms mediating aggressive behaviors has to await the development of selective agonists and antagonists, respectively.

Aggression↗
PubMed1987

Postpartum aggression in rats does not influence threshold currents for EBS-induced aggression.

Female Wistar rats were tested for aggressive behaviour induced by electrical brain stimulation (EBS) in the lateral hypothalamus. Threshold currents for the induction of aggression were determined on several days before the females were paired with experienced breeder males. Beginning in the second week of pregnancy threshold current values were measured once or twice weekly. No change in thresholds was observed either during pregnancy, the early postpartum period or after weaning. Lactation was the only period during which the females were spontaneously aggressive towards male intruders in their home cage, but not in the EBS cage. Analysis of bite targets revealed no difference between the bite patterns in the postpartum maternal aggression test and the EBS-induced attacks. The results demonstrate that the change in physiological and hormonal status in pregnant and lactating females has no influence on the propensity to attack during EBS. The similarity in wound patterns does not advocate a major difference in the types of aggression studied. We speculate upon the nature of EBS-induced attacks as the activation of a rigid, final pathway of aggression which is rather insensitive to mild modulations.

Aggression↗
PubMed1987

Modulatory actions of benzodiazepine receptor ligands on agonistic behaviour.

Several experiments were conducted to establish the role of benzodiazepine (BDZ) receptor ligands in aggressive behaviour in male and female rats. In particular, the pro-aggressive effects of BDZ agonists was subject of investigation. Predatory aggression (mouse killing) was facilitated by chlordiazepoxide (CDP) when tested in naive female rats, but CDP was unable to induce muricide in non-killing rats with extensive experience with mice. In experiments on maternal aggression in rats a post-hoc analysis revealed that the pro-aggressive action of CDP on maternal aggression was base line dependent: the increase in aggression in spontaneously low aggressive females was significantly higher than in females with a higher base line level. A further study aimed at unravelling the underlying factors contributing to this pro-aggressive action by determining the role of opponent size on the effects induced by CDP. Normally large opponents evoke less aggression from lactating females than smaller opponents and CDP exerted its pro-aggressive effect particularly strongly in the 'large opponent' situation. An ethological analysis was made of lateral display--an ambivalent posture frequently occurring in agonistic behaviour--to establish whether CDP indirectly increases aggression by reducing fear by means of its anxiolytic properties. The data partly support this hypothesis. These findings stress the importance of environmental and experiential factors in the possible outcome of CDP effects on aggression. Moreover, they point to possible explanations of seemingly contradictory data. In two final experiments an inverse benzodiazepine receptor agonist (beta-CCE) was tested in maternal aggression. beta-CCE reduced aggression, although not in a completely specific way. A neutral BDZ-receptor antagonist (Ro 15-1788) was tried in an attempt to antagonize the pro-aggressive effects of CDP in maternal aggression. Ro 15-1788 did not counteract the pro-aggressive action of CDP, but antagonized CDP effects on exploration. The modulatory role of the benzodiazepine receptor complex in aggression remains an intriguing area of research in which many subtleties in testing conditions play a role and in which more BDZ agonists, inverse agonists and antagonists have to be tested.

Aggression↗
PubMed1987

Analysis of survival data on aging rat cohorts: pitfalls and some practical considerations.

Experimental aging research is very dependent on the determination of the survival characteristics of the animal species or strain under study. Such data are generally inferred from mortality curves of cohorts of animals that are set aside at an early age for aging studies. Rectangular survival curves and the presence of multiple pathological lesions are a prerequisite for aging studies so as to resemble the situation in man. From 1977 onwards, many rat cohorts have been formed in the Institute for Experimental Gerontology (IVEG) for the study of aging processes. Data from these have been analysed for a period of 5 years up to and including 1982. (Males and females of the WAG/Rij and BN/BiRij strains were used.) The 50% survival and the maximum survival of cohorts varied considerably, but showed no consistent trend over the years. The median (50%) survival between the cohorts differed by as much as 7.9-10.7 months for the strains and sexes studied. Maximum survival between the cohorts varied from 3.7 to 9.9 months. Median and maximal survival were greater for the females. Maximum survival and 50% survival correlated significantly, the relation between the two being approximately linear. The effect of removing animals from cohorts on the estimation of 50% survival was only minor, whereas maximum survival was clearly diminished by this procedure. The wide variation in survival characteristics, even between successive cohorts, cautions against too simple a measure of the animals survival in only one number for median or maximal survival in months. An indication of the variance of 50% survival and of maximum survival should therefore be included in scientific publications. Moreover, the 50% survival is the parameter of choice to define cohorts, not only because this can be most reliably estimated with good confidence limits, but also because this measure is the least sensitive to removing animals from the cohorts. As this will often be the case in many research institutions, it might be of practical importance to order old animals from different cohorts since this diminishes the chance of using an extremely short or long lived cohort. Finally, the analysis revealed that combining intact or incomplete cohorts into larger survival curves resulted in nearly identical graphs. An attempt was made to calculate the minimum cohort size which yields survival curves with constant 95% confidence limits.

Aging↗
PubMed1987

Maternal aggression towards different sized male opponents: effect of chlordiazepoxide treatment of the mothers and d-amphetamine treatment of the intruders.

Lactating female rats vigorously attack equally sized conspecific males introduced into their home cage. Under conditions of such high aggression, the previously reported pro-aggressive action of a low (5 mg/kg) dosage of chlordiazepoxide (CDP) is hardly detectable. When opponents are large, the intensity of the aggression is less than what is seen with small ones. In this situation treatment of the females with CDP increases aggression levels substantially. The importance of intruders evoking aggression was further investigated by treating different sized opponents with d-amphetamine. d-Amphetamine treatment did not lead to major changes in the defensive capacities of either types of intruder. The data demonstrate that drug effects, such as pro-aggressive actions, may be observed using larger sized opponents that are not so easily defeated and show more adequate defense than small ones. The subtleness of the dyadic interactions in maternal aggression indicates that drug effects should be considered carefully before extrapolation to other conditions.

Aggression↗
PubMed1986

RO 15-1788 does not influence postpartum aggression in lactating female rats.

Recently, Hansen et al. (1985) suggested behavioural similarities between lactating rats and non-maternal rats treated with benzodiazepines (BDZ), indicating that lactation may be associated with an increased activity state at the GABA/BDZ receptor complex similar to BDZ treatment. A logical prediction of this hypothesis is that BDZ antagonists should decrease typical maternal behaviours involved, such as aggression. We tested this hypothesis by measuring the behavioural effects of the BDZ antagonist RO 15-1788 (1.25-10 mg/kg IP) on aggressive behaviour of lactating female rats confronted with male intruders. We could not support the hypothesis; no consistent behavioural effects of RO 15-1788 on aggression were found. The implications of this finding for the proposed hypothesis are discussed.

Aggression↗
PubMed1986

Maternal aggression in rats: lack of interaction between chlordiazepoxide and fluprazine.

In a paradigm of female aggression, maternal aggression, low doses of chlordiazepoxide (CDP) enhanced aggression, whereas the serenic drug fluprazine dose-dependently decreased aggression. In this study one selected dose of CDP (5 mg/kg PO) clearly enhanced aggression of female lactating rats against a naive male intruder. This dose of CDP however, was not able to antagonize the dose-dependent decrease observed after fluprazine treatment (5, 10, 20 mg/kg IP). These data suggest that fluprazine and CDP do not simply have opposite effects at the same site of action. It is suggested that fluprazine decreased the offensive motivation of animals, whereas CDP increased attacks indirectly by reduction of the approach-avoidance conflict in a social context.

Aggression↗
PubMed1985

Maternal aggression in rats: effects of chlordiazepoxide and fluprazine.

Although maternal aggression in rats is confined to a restricted post-partum period, the high and stable aggression level and the constancy of its behavioural structure make it an attractive experimental procedure for studying the behavioural effects of psychotropic drugs. Female rats were tested against naive male intruder rats for 5 or 10 min on post-partum days 3-9, during which aggression is stable. Chlordiazepoxide (CDP; 5, 10 and 20 mg/kg, orally) had a biphasic effect on aggression; it increased aggression considerably at 5 and (to a lesser extent) at 10 mg/kg. At 20 mg/kg aggression returned to control level. CDP shortened the latency to the first attack at 5 mg/kg, but not at higher dosages. CDP enhanced aggression, particularly in the first 2 min of an encounter. It did not change the structure of the aggressive behaviour, but did induce a dose-dependent increase in feeding. Fluprazine (Flu; 5, 10 and 20 mg/kg IP), a specific antiaggressive (serenic) drug, induced a dose-dependent decrease in aggression and exerted its largest effect in the first 2 min of an encounter. In accordance with the reduced aggression, latencies to the first attack increased. Maternal aggression in rats represents an extension to other (male) aggression paradigms in psychopharmacology. First, it has no male counterpart. Secondly, the hormonal mechanisms underlying this behaviour differ from those of male aggression. Thirdly, the morphology of maternal aggression is different from that shown in male models of agonistic behaviour (e.g. resident-intruder). These features make maternal aggression an attractive paradigm for pharmacological studies of female behaviour.

Aggression↗
PubMed1984

Different test situations for measuring offensive aggression in male rats do not result in the same wound pattern.

It has been reported by the Blanchards, that the attacks of offensively motivated rats produce a very characteristic wound distribution on the body of opponents, the back region being the most prominent target area. We now report that the distribution of wounds on male intruders produced by male resident Wistar rats in a resident-intruder paradigm, depends on the experimental situation used. Rats solitarily housed in small cages (0.1 m2), produced most wounds (57%) on the upper back, about 14% on the lower back, whereas head and belly were much less bitten. Rats housed in larger cages (0.52 m2) with a female ("territorial situation") produced about 39% of the wounds on the back, equally divided over the anterior and posterior parts. In this situation the head (21%) and the belly (23%) were more frequently bitten than in the other test situations. In a large colony (5.7 m2), practically all wounds were situated dorsally (81%), the majority (58.5%) on the lower part of the back. It was concluded that the distribution of wounds over the body of the intruder was at least partly determined by the possibility of escape.

Aggression↗