Journal Article

Symposium 25 Tuesday Sept. 25th 1.30 pm–3.00 pm; Room: Lecture Hall 1

in Alcohol and Alcoholism

Volume 42, issue suppl_1, pages i24-i25
Published in print August 2007 | ISSN: 0735-0414
Published online January 2007 | e-ISSN: 1464-3502 | DOI: https://dx.doi.org/10.1093/alcalc/agm100
Symposium 25 Tuesday Sept. 25th 1.30 pm–3.00 pm; Room: Lecture Hall 1

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One goal of behavioral neuroscience is to understand the biological mechanisms underlying brain function and behavior and their changes in pathological conditions. An ethoexperimental approach in the study of behavior aims at the use of biologically relevant laboratory test environments and to include descriptions of the animal's behavior as part of the analysis in the study of meaningful behaviors.

This symposium will cover basal considerations that are important to keep in mind when working with animal models of human symptoms and disorders (Meyerson BJ). What represents a good model? How often is anthropomorphism a problem when trying to model human disorders in animals? The following presentations will cover rodent behavior models for assessment of behavioral profiles as well as specific behavioral traits of relevance for reinforcing mechanisms, e.g. implicated in the vulnerability for alcohol dependence (Roman E and van den Bos R). The final presentation will describe a non-human primate model of adverse early-life rearing conditions that has been used to study how genetic variants interact with social factors, temperament and alcohol response as motivating factors for alcohol consumption (Wargelius, HL).

The presentations on animal behavior models will cover models for mice, rats and non-human primates.

Conclusions. There is a continuous demand for new and improved tests for experimental animals in the field of behavioral neuroscience. Relevant behavioral markers will improve the understanding of mental functions and dysfunctions, e.g. mechanisms underlying individual differences in the vulnerability for alcohol dependence.

Presentation S25-1

Basal considerations when using animal models

Meyerson B (Sweden)

Aims. Parallel to the progress in genetics, cell biology and drugs targeting the nervous system there is a requirement for behavioral markers in order to gain an understanding of mental functions and dysfunctions. The choice of models has to balance controlled laboratory conditions and to meet reasonable criteria from an ethological viewpoint. Difficulties in implementing reliable behavioral analyses also constitute the problem whether the animal behavior measured corresponds to the aimed human mental state. That is the issue to be discussed.

Methods. Irrespective of whether the purpose is screening, functional phenotyping or has its focus directed on a particular predetermined mental condition such as drug dependence, traditionally either a battery of tests or multivariate designs are used. By multivariate is meant that the subject has a free choice of different environments contained in the same test arena. To evaluate drug dependence in terms of drug seeking and consumption require an estimate of what is specifically related to the mental state of dependence and how this relates to personality traits.

Results. Behavior is the stimulus elicited integrated result of a neuronal process based on the interplay between what is evolutionary founded and what has become acquired by experience. There is a great diversity as to species specific behavioral strategies which contrasts to the inter species conformity on a cell biological basis. The presentation will bring up examples and discuss methodological complex of problems related to anthropocentrism in evaluation of human mental conditions from animal data.

Conclusions. A methodological approach based on an ethological perspective is stressed. The advantage of multivariate designs and besides conventional statistics, the access to multi-variate data analysis (Principle Component Analyses) should be considered.

Presentation S25-2

The multivariate concentric square field test for behavioral profiling in rodents

Roman E (Sweden)

Aims. Alcohol dependence is a heterogeneous disorder and the individual vulnerability to develop alcoholism is determined by the combination of several factors including personality trait characteristics, genetic and environmental factors. A demand for an improved understanding of the neurobiological basis underlying dependence disorders, e.g. alcoholism, especially with regard to motivational aspects, has recently been highlighted. Animal behavior experiments are justified to understand the biological basis for human mental disorders. There is a demand for improved models in behavioral neuroscience. Therefore, relevant and validated animal models seem important.

Methods. The recently established multivariate concentric square field (MCSF) test is a technique with an ethoexperimental approach that in one and the same test situation includes a variety of physical situations meaning risk, safety, exploratory incentives etc. that permit measurements of general activity, exploration, approach/avoidance in open versus sheltered areas and the motivation for seeking reinforcers. The purpose of the multivariate design is to gather information that taken together should illustrate a personality profile including how this profile is altered under various forms of challenges.

Results. The human typologies of alcoholism include assessment of anxiety, impulsiveness and novelty seeking. The MCSF generates a behavioral profile including aspects of those mental states and behaviors and seems to be very well suited for characterization of behavioral profiles of relevance for dependence disorders.

Conclusions. The use of the MCSF test in the behavior characterization of alcohol-preferring and non-preferring rats as well as in studies of motivation of relevance for reinforcement will be discussed.

Presentation S25-3

The Iowa Gambling Task: from humans to animals and back

Van den Bos R (Netherlands)

The Iowa Gambling Task (IGT) in humans is in principle suited to study long-term efficiency of behaviour in a biologically relevant context. Key features of this task are uncertainty of outcomes and a conflict between the immediate and long-term pay-off of options. At a neurobehavioural level the IGT measures the interaction between reward and cognitive control. Animal models allow for studying the underlying neurobiology of decision-making processes and long-term efficiency of behaviour in more detail and at greater depth than possible in humans. Therefore we set out to develop a model of this task in rodents using the task's key features. The data thus far suggest that in the rodent IGT mice and rats behave similar to humans. An important cross species finding is that females tend to balance short-term and long-term interests whilst males focus more on long-term interests. In a recent experiment using rats in which the serotonin reuptake transporter (SERT) was knocked out we observed that both homozygous and heterozygous SERT female rats showed a performance similar to male rats. This prompted us to study the SERT polymorphism in women with respect to the IGT as well as eating disorders, which are related to this polymorphism. The data show that by going back and forth between humans and animals using the same model we gain insight into the dynamics underlying decision making processes and into the liability of individuals to engage in addictive behaviour.

Presentation S25-4

Behavioural profiles and gene × environment interactions related to alcohol intake in rhesus monkeys

Wargelius HL, Newman TK, Barr C, Oreland L, Higley JD (Sweden)

Aims. A non-human primate model of adverse early-life rearing has been used to study how genetic factors interact with social factors to predict alcohol consumption. Behavioural phenotypes of the monkeys are presented in light of their genetic makeup and rearing background.

Methods. Rhesus monkeys reared with or without the influence of adults have been assessed for impulsive and aggressive behaviours both in the home cage environment and in special challenges targeting those behaviours. At the age of 4 years, the monkeys were enrolled to a free-access alcohol paradigm where voluntary alcohol consumption was measured. Platelet MAOB activity as a marker of central serotonergic activity has been investigated together with functional variants of serotonergic genes in the monkeys (i.e. rhMAO-A, rh5-HTT).

Results. Serotonergic genes in rhesus monkeys, functionally equivalent to those increasing vulnerability for deviant behaviour in humans, interacted with rearing condition for behaviours related to impulsivity and aggression. Pronounced sex differences were seen in the response to rearing and in the behavioural profiles as well as with regard to the different gene variants.

Conclusions. Early environmental trauma, here demonstrated with a rearing model, had a great impact on the behavioural profile of the monkeys. In addition a weak serotonergic system, as indicated by low platelet MAO activity and presence of the low functioning rhMAO-A and rh5-HTT alleles, interacts with such trauma to precipitate certain behaviours that in turn are related to proneness for higher alcohol consumption. In short, genes, environment and sex are important factors for behavioural traits underlying risk for high alcohol consumption.

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Subjects: Public Health and Epidemiology

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