Selectively Bred Rodents as Models of Depression and Anxiety

Abstract

Stress related diseases such as depression and anxiety have a high degree of co morbidity, and represent one of the greatest therapeutic challenges for the twenty-first century. The present chapter will summarize existing rodent models for research in psychiatry, mimicking depression- and anxiety-related diseases. In particular we will highlight the use of selective breeding of rodents for extremes in stress-related behavior. We will summarize major behavioral, neuroendocrine and neuronal parameters, and pharmacological interventions, assessed in great detail in two rat model systems: The Flinders Sensitive and Flinders Resistant Line rats (FSL/FRL model), and rats selectively bred for high (HAB) or low (LAB) anxiety related behavior (HAB/LAB model). Selectively bred rodents also provide an excellent tool in order to study gene and environment interactions. Although it is generally accepted that genes and environmental factors determine the etiology of mental disorders, precise information is limited: How rigid is the genetic disposition? How do genetic, prenatal and postnatal influences interact to shape adult disease? Does the genetic predisposition determine the vulnerability to prenatal and postnatal or adult stressors? In combination with modern neurobiological methods, these models are important to elucidate the etiology and pathophysiology of anxiety and affective disorders, and to assist in the development of new treatment paradigms.

Differential postpartum sensitivity to the anxiety-modulating effects of offspring contact is associated with innate anxiety and brainstem levels of dopamine beta-hydroxylase in female laboratory rats

“…For instance, intracerebroventricular infusion of corticotropin-releasing factor cannot increase anxiety in female rats that are already highly anxious (Klampfl et al, 2013). On the other hand, anxiolytic drugs cannot further decrease anxiety in already low-anxious animals (Wegener et al, 2012). …”

The Flinders Sensitive Line Rat Model of Depression—25 Years and Still Producing

“…In fact, there are so many models that it is not possible to do justice to them all; the reader may consult Overstreet (2012) and Wegener et al (2012) for further details. The Wistar Kyoto (WKY) rat is a control rat bred in parallel to the spontaneously hypertensive rat, but Pare (1989Pare ( , 1992) noted a number of behavioral abnormalities.…”

Pharmacological Effects of Lu AA21004: A Novel Multimodal Compound for the Treatment of Major Depressive Disorder

“…Regarding animal models, the Flinders Sensitive Line (FSL) rat and its control counterpart, the Flinders Resistant Line (FRL) rat, have been selectively bred for high and low sensitivity to cholinergic agonism, respectively (Wegener et al, 2011). The cholinergic hypersensitivity gives rise to changes in other neurotransmitter systems, because the FSL rat has lower density of 5-HT 1A receptors but a higher density of 5-HT 1B receptors in several brain regions compared with those of the FRL rat (Nishi et al, 2009).…”

“…The cholinergic hypersensitivity gives rise to changes in other neurotransmitter systems, because the FSL rat has lower density of 5-HT 1A receptors but a higher density of 5-HT 1B receptors in several brain regions compared with those of the FRL rat (Nishi et al, 2009). In the rat forced swim test, FSL rats display depressive-like behavior that is reversed by antidepressants (Wegener et al, 2011). The rat social interaction test is a widely used assay that assesses the time two unfamiliar rats spend actively interacting in a novel aversive environment; compounds that have anxiolytic properties increase that time (File and Seth, 2003).…”