Intra-adrenal mechanisms in the response to chronic stress: investigation in a rat model of emotionality

Abstract

The exploratory behaviour of the genetically derived Maudsley rat model of emotionality has been well characterized. Maudsley reactives (MR) present with more 'anxious-like' behaviour than Maudsley nonreactives (MNR). Although this behaviour is assumed to be associated with altered adrenocortical function, the few studies addressing this issue have produced inconsistent findings. We therefore set out to investigate the adrenal endocrinology of the MR and MNR strains. Control Wistars, the ancestors of the Maudsleys, have been used for the first time to set the baseline for all the experiments carried out. It was found that the MNR strain had a significantly blunted adrenocorticotrophic hormone (ACTH) response to restraint stress compared with Wistars, but a normal corticosterone response. Conversely, the MR had a significantly exaggerated ACTH response to restraint stress, but a normal corticosterone response. This finding suggested that the MR adrenal is less sensitive to ACTH than the MNR. This was confirmed by investigating the corticosterone dose-response to ACTH in adrenals from the two strains incubated in vitro. Several possible intraadrenal regulators were investigated, but the only significant molecular difference in the adrenal glands from the two strains was the level of expression of neuropeptide Y (NPY), which is known to be a stress-responsive peptide in the adrenal. We propose that intra-adrenal NPY is responsible for blunting adrenocortical responses to ACTH stimulation in the MR strain. The observed changes in adrenal NPY suggest that this rat strain may serve as a model of chronic stress, with the MR phenotype representing maladaptation.

Effect of acute swim stress on plasma corticosterone and brain monoamine levels in bidirectionally selected DxH recombinant inbred mouse strains differing in fear recall and extinction

“…In another genetically derived model of emotionality, Maudsley rats did not differ in their peripheral corticosterone response to acute restraint stress, although the more reactive strain exhibited a stronger adrenocorticotropic hormone (ACTH) response than the less reactive strain. The blunted corticosterone response to ACTH in the more reactive strain resulted from an adaptation of the adrenal cortex (Kosti et al, 2006). In high (HAB) and low anxiety behavior (LAB) rats bidirectionally selected in the elevated plus maze paradigm, the reactivity of the HPA axis/corticosterone response to various stressors correlated with a polymorphism in the arginin-vasopressin promoter, resulting in a potentiated vasopressin release.…”

Some physiological and biochemical methods for acute and chronic stress evaluationin dairy cows

“…However, to elicit a distress chronIc StreSS evaluatIon In cattle response, a stressor must be perceived as dangerous factor by the animal, causing deleterious effects (Moberg, 2000). The perception can be vary depending on the genetic background, previous experiences, the psychological context of the stress (Mormède and Dantzer, 1988;McEwen, 1998;Romero, 2004;Kosti et al, 2006), the age (Romero, 2004), the types and the duration of the stressors. Based on these the final response will also vary.…”

“…The major factors include the following: environmental (season, temperature), physiological (milk yield, age, and stage of lactation; Hasegawa et al, 1997;Bertoni et al, 2006a) and genetic (Weiss et al, 2004;Kosti et al, 2006). One of more intriguing aspects has been shown by Kosti et al (2006), who found an exaggerated ACTH release to restraint stress (30 minutes), but only a slightly higher (NS) rise of corticosterone, in a strain of rat characterised by more 'anxious-like' behaviour in comparison to a nonreactive strain. These results could in fact suggest a lower sensitivity of the adrenal gland during stress in 'anxiouslike' subjects, but they could also imply the achievement of a plateau of the plasma cortisol level, therefore independentabove a certain threshold -to the degree of the ACTH stimulus.…”

Neuroendocrine pathways in benzodiazepine dependence: new targets for research and therapy

“…Therefore it has been suggested that NPY probably suppresses increased CRH levels via the protein kinase A pathway ( (Sajdyk et al, 2004) for review). In line with its anxiolytic effects and this hypothetical CRH antagonism central application of low doses of NPY has been reported to reduce ACTH and cortisol secretion (Harfstrand, 1987;Heilig, 1994) in adrenocortical cells (Kosti et al, 2006;Lesniewska et al, 1990;Malendowicz et al, 1990) and in healthy volunteers (Antonijevic et al, 2000). Figure 1 illustrates this hypothetical relationship between NPY and CRH.…”