A successful survival for any individual depends on their ability to cope with numerous environmental stressors and challenges. For that purpose, an organism is equipped with a number of regulatory mechanisms. The two main components of the stress system are (1) the HPA (HPA) axis and (2) autonomic nervous system (ANS) (especially the sympathetic branch).
The most important central component of the HPA axis is the paraventricular nucleus (PVN) of the hypothalamus (encompassing both corticotropin-releasing factor (CRF)-containing neurons and neurons containing arginine-vasopressin (AVP)). The PVN is under tight control of the hippocampal formation (Chrousos, 1998). It is generally assumed that the hippocampus inhibits the PVN through its connection with the bed nucleus of the stria terminalis (Cullinan et al., 1993). The principal target of the CRF cells in the PVN are the
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Fax: +31-24-3540044; E-Mail: A.Ellenbroek(a:pnf.umcn.nl adrenocorticotrophin hormone (ACTH)-containing cells within the pituitary gland. The simultaneously released AVP act synergistically with CRF, though it is hardly effective by itself. ACTH, in turn, specifically acts on the adrenal cortex to stimulate the production and release of glucocorticoids, such as corticosterone in rats or Cortisol in humans. These glucocorticoids represent the final effectors of the HPA axis, and in turn regulate the release of CRF and ACTH, via multiple negative feedback mechanisms.
The second major limb of the stress response system is the ANS, which consists of a sympathetic and a parasympathetic branch. Stressors lead to activation of the sympathetic nervous system and in some cases to a suppression of the parasympathetic nervous system. This leads to an increase in, among others, heart rate, blood pressure, breathing and body temperature. The major central components of the ANS are the locus coeruleus (LC), and adjacent cell groups of the medulla and the pons, especially the nucleus of the solitary tract (NTS), which direct the ANS. The NTS, which receives information from virtually all major organs in the body including the baroreceptors on the carotid arteries and aorta, which play a crucial role in regulating blood pressure. It has numerous reciprocal connections with many structures involved in regulating the stress response, such as the parabrachial nucleus, the central nucleus of the amygdala and multiple hypothalamic structures. In addition the NTS projects to the medulla (especially the caudal and rostral ventrolateral medulla), which are crucially important in regulating the cardiovascular system and to the intermediolateral column, which contains the preganglionic cell bodies of the sympathetic nervous system (Gabella, 1995; Saper, 1995; Colombari et al., 2001).
It is important to realise that these two systems are intimately linked to each other. For instance, the LC and the NTS system receive input from and project to the PVN (Aston-Jones et al., 1995; Saper, 1995). Moreover, these structures contain a dense population of CRF and AVP receptors and the intracerebral injection of CRF can reproduce the full spectrum of behavioural and peripheral symptoms of a natural stress response, including the activation of the sympathetic nervous system.
In addition to these two principal systems, the stress response also directly interacts with accessory systems, such as the amygdala and the mesolimbic and mesocortical dopaminergic system (Chrousos, 1998). The amygdala, especially the central nucleus of the amygdala, is intimately linked with the stress system and project to the PVN (Gray et al., 1989), the LC (Cedarbaum and Aghajanian, 1978) and the NTS (Schwaber et al., 1982), and thus can activate both the HPA axis and the ANS system. The mesolimbic and mesocortical dopaminergic system are also closely linked to the regulation of stress (Finlay and Zigmond, 1997). Thus most stressors, including novelty stress (Saigusa et al., 1999), restraint or footshock (Imperato et al., 1991; Puglisi-Allegra et al., 1991) increase the extracellualr dopamine concentrations in the nucleus accumbens. The cell bodies of these neurons are located in the ventral tegmental area (A10 cell group) and receive inputs from the LC and the central nucleus of the amygdala (Oades and Halliday, 1986). Moreover, the A10 cell group contains glucocorticoid receptors (Harfstrand et al., 1986), and corticosteroids enhance the dopaminergic transmission
(Piazza et al., 1996). In addition dopaminergic receptors activate the CRF-containing PVN cells (Eaton et al., 1996).
Even though the stress system is tightly regulated and plays an essential role in maintaining the homeostasis in an organism, there are large individual differences in the amplitude and duration of the stress response. Such differences are undoubtedly due to a combination of specific genetic and (early) rearing conditions. As discussed elsewhere in this book (...) early environmental manipulations can permanently alter the set point of the HPA axis (Levine, 1994; Rots et al., 1996b; Workel, 1999). Much less is known about the influences of early rearing conditions on the sensitivity of the ANS, although cross-foster studies clearly point to a role for maternal influences on blood pressure (see below).
To gain insight into the role of genetic factors in regulating the stress response, genetically different rat strains are a valuable tool. Many different strains of rats have been described, many of which have been compared to others especially in relation to HPA axis activity. The aim of the present chapter is to give an overview of the most important rat strains and strain comparisons in the field of stress research. As in most other (neuro)biological research, large differences in techniques and results (especially absolute values) exist between different laboratories. This makes it difficult to compare the stress-sensitivity of different strains across laboratories. We have therefore decided to focus primarily on those papers in which two or more strains are directly compared, and have refrained from comparing results across different papers and laboratories.
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