An evolutionary approach to behavioral pharmacology: using drugs to understand proximate and ultimate mechanisms of different forms of aggression in mice

Q1 · PSYCHOLOGY

Review

Author: Stefano Parmigiani ; Paola Palanza ; Pier Francesco Ferrari

Psychoactive drugs (Fluprazine and Chlordiazepoxide--CDP) were used as probes to test both differences or similarities in neurochemical substrates (proximal causations) and adaptive significance (ultimate causations) of different forms of intraspecific aggression in wild mice and laboratory Swiss CD-1 counterparts. Fluprazine (1-5 mg/kg) inhibited maternal attack on female, but not on male intruders. Thus, phenotypically different attack behaviors (offence and defence respectively) which have different functions may be modulated by different neurochemical substrates. Intrasexual attack and infanticide which are phenotypically different, but share similar functions (i.e. competition for mates and resources) were equally inhibited by Fluprazine (2 mg/kg) both in males and females of wild and laboratory mice. This indicates that the neural substrates of these behaviors are related and similarly regulated in the two sexes. Fluprazine was used to test the prediction of the evolutionary model on fighting strategies in male-male asymmetric contests as far as fighting ability and resource value (mating and cohabitation with a female) are concerned. Fluprazine inhibited the intensity of fighting (i.e. more 'defensive' behavioral phenotype of attack) only in animals without previous positive fighting experience, suggesting that different behavioral strategies are based on different neurochemical modulation. Experience of attack also influenced the effects of CDP (2.5-5 mg/kg) in both lactating females and male resident mice. The reported proaggressive effects of benzodiazepines were observed only in animals with prior fighting experience in both cases. Thus the understanding of the effects of drugs on behavior demands consideration of the biological variability (e.g. genetic, previous experience and/or interindividual differences) and the adaptive significance of behavior in the experimental context. On this background ethopharmacology can be defined as an evolutionary approach to the study of a drugs effect on neurochemical mechanisms and functions of behavior.

01 Aug 1996·Physiology & BehaviorQ3 · MEDICINE

Comparing different forms of male and female aggression in wild and laboratory mice: An ethopharmacological study

Q3 · MEDICINE

Article

Author: S. Parmigiani ; R.J. Rodgers ; Pier F. Ferrari ; M. Mainardi ; P. Palanza

The purpose of this study was to compare the effects of 2 mg/kg fluprazine (a serotonergic psychoactive drug with antiaggressive properties) on intrasexual attack, infanticide, and predation (on an insect larva) in males and females of wild and Swiss mice. The results showed that, in both stocks of mice, fluprazine significantly inhibited intrasexual and infanticidal attack in both sexes, but predatory attack was not altered by the drug treatment. Motivational and neural substrates underlying intrasexual attack and infanticide appear, thus, to be related to each other, and similarly modulated in both males and females. Conversely, predatory attack seems to be under a different neurohumoral control. The similar regulation of proximal mechanisms of aggressive behavior observed in wild and Swiss mice suggests a common neurobiology of aggression. For this reason, the outbred laboratory Swiss mice appear to be a reliable model for studies on causal and functional mechanisms of aggression.

01 Dec 1992·Behavioural PharmacologyQ4 · PSYCHOLOGY

Anxiogenic-like effects of fluprazine and eltoprazine in the mouse elevated plus-maze

Q4 · PSYCHOLOGY

Article

Author: Wallis, P. ; Doran, P. J. ; Rodgers, R. J. ; Cole, J. C. ; Cobain, M. R. ; Eells, J. R. ; Daly, P.

It has recently been proposed that the "serenic" (antiaggressive) agents, fluprazine and eltoprazine, may enhance fear/anxiety reactions in laboratory rodents. In the present study, the influence of these compounds (1.25-10.0mg/kg) on anxiety-related behaviour in male mice was examined in the elevated plus-maze test. For comparative purposes, the effects of 8-OH-DPAT (0.01-1.0mg/kg) CGS 12066B (1.25-10mg/kg), TFMPP (0.63-5.0mg/kg) and mCPP (0.5-4.0mg/kg) were also assessed. Behavioural analysis incorporated not only traditional parameters but also several novel measures of defensive behaviour (i.e. "risk assessment"). The selective 5-HT(1A) agonist 8-OH-DPAT produced effects only at 1.0mg/kg, with evidence of an anxiolytic/sedative action at this dose. In the absence of other behavioural changes, CGS 12066B (a selective 5-HT(1B) agonist) caused a preferential and dose-dependent (2.5-10.0mg/kg) stimulation of closed arm entries, an effect also seen with low doses of TFMPP (0.63mg/kg) and the serenics (1.25-2.5mg/kg). In addition, both TFMPP and mCPP (5-HT(1C/1B) agonists) induced dose dependent anxiogenic-like effects over the dose ranges tested, with the most pronounced changes observed on measures of risk assessment. The profiles of fluprazine and eltoprazine on plus-maze behaviour were not only similar to one another but, on most parameters, were also remarkably like those observed with TFMPP and mCPP. These data question the behavioural selectivity of the serenics and further support the proposal that these compounds may potentiate anxiety. Findings are discussed in relation to underlying receptor mechanisms, and the utility of a more ethological approach to the analysis of behaviour on the elevated plus-maze.

100 Deals associated with Fluprazine

External Link

KEGG	Wiki	ATC	Drug Bank
-	Fluprazine	-	-

R&D Status

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis