Development of divergence in dopamine responsiveness in genetically selected rat lines is preceded by changes in pituitary-adrenal activity

Abstract

A b s tra c tTwo pharmacogenetically selected Wistar rat lines have been used as a model for individual variability in behavioral and neuroendocrine responses. As a selection criterion the behavioral responsiveness For the dopamine agonist apomorphine was used, giving rise to the apomorphine-susceptible (apo-sus) and apomorphine-unsuseeptible (apo-unsus) rat lines. This selection has been maintained over 16 generations. Recent studies have shown that adult rats of these selection lines also show pronounced differences in responsiveness of the hypothalamic-pituitary-adrenal (HPA) system. In this study we analyzed to what extent the divergence in dopamine phenotype and HPA responsiveness, as observed in adult rats, are linked to possible differences, within both systems, during early postnatal development. Therefore, we measured in neonatal female rats of 10 and 18 days of age several parameters of the dopamine and UFA system which show significant differences in adult rats. These include tyrosine hydroxylase (TH) and dopamine D1 and D2 receptor mRNA levels, which were determined within the nigrostriatal system since this system shows the most pronounced differences hot ween adult rats oF both selection lines. As indices of HPA activity we measured CRH mRNA, ACTH and total and free corticosterone plasma concentrations under basal conditions in the morning. Transcripts of the two types of corticosteroid receptors, mineralocorticoid (MR) and glucocorticoid (GR) receptor were measured in hippocampus and paraventricular nucleus. In 10-day-old rats all dopamine and MPA parameters were similar in rats of the two selection lines, except for GR mRNA in the parvocellular neurons of the paraventricular nucleus of the hypothalamus (PVN) of apo-sus rats, which was significantly higher than in apo-unsus rats. Highteeu-day-old apo-sus rats, however, showed significantly higher ACTH, comparable total corticosterone and a trend towards lower Free corticosterone plasma levels. This HPA profile resembles the situation in adult apo-sus rats as compared with adult apo-unsus rats. Hippocampal GR mRNA expression and thymus weight were also higher in apo-sus rats. In addition, these rats showed an age-related increase in hippocampal MR mRNA expression, while in apo-unsus rats M R mRNA levels did not change between pnd 10 and 18. The measures of the nigrostriatal dopfimme system at day 18 were still similar in rats oF both lines. In conclusion, divergence in the dopamine systems of the two pliarmaeogenetieally selected rat lines emerges subsequent to divergence in pituitary-adrenal activity.

Adrenocortical reactivity and central serotonin and dopamine turnover in young chicks from a high and low feather-pecking line of laying hens

“…Furthermore, it was shown that corticosteroids via GRs may play an important role in the sensitization of the DA system [37]. Interestingly, the development of divergence in DA responsiveness in apomorphine susceptible and unsusceptible rat lines, that also differ in coping strategy, is preceded by changes in pituitary -adrenal activity [38].…”

“…Consequently, corticosteroids may alter neural transmission in the serotonergic (5-hydroxytryptamine, 5-HT) [35] and dopaminergic (DA) system [32]. Indirectly, it has been shown that 5-HT as well as DA neurotransmission is altered in adult proactive individuals compared to adult reactive individuals [27,38].…”

The effects of stress on alcohol consumption: mild acute and sub-chronic stressors differentially affect apomorphine susceptible and unsusceptible rats

“…As mentioned in the introduction, the APO-SUS rats are characterized by higher levels of TH immunoreactivity in the ventral striatum (Van der Elst et al, in press a), a higher amount of dopaminergic D2 receptors in the striatum (Rots et al, 1996), a functionally lower noradrenergic activity in the ventral striatum (Ellenbroek and Cools, 1993;Cools et al, 1990), and lower free plasma levels of corticosterone (Rots et al, 1995) than the APO-UNSUS rats. All these features are associated with less alcohol consumption (Stefanini et al, 1992;Gongwer et al, 1989;Gongwer et al, 1989;Murphy et al, 1982;Casu et al, 2002;Mcbride and Li, 1998;Taylor et al, 1990;Murphy et al, 1987), and this study therefore gives more weight to this correlation.…”

“…The differential response of the APO-SUS and the APO-UNSUS rats to the acute challenge can be attributed to the interline differences in the reactivity of their HPA axis. APO-SUS rats are marked by a higher and prolonged stress-induced response of the HPA-axis, as measured by the release of ACTH and corticosterone (Rots et al, 1996;Cools et al, 1990), which might explain why the relatively stress-sensitive APO-SUS rats have a strong and long-term increase in alcohol consumption after the acute challenge, whilst the stressinsensitive APO-UNSUS rats have a small and short-term increase in intake. Alternatively, the noradrenergic activity of the ventral striatum might also be involved in the stress-induced change in consumption.…”

“…Subsequent selective breeding has resulted in two distinct rat types that are divergent in the structure and function of, amongst others, the dopaminergic and noradrenergic system and the stress sensitivity. Under non challenged conditions, the APO-SUS rats are characterized by higher levels of TH immunoreactivity in the ventral striatum (Van der Elst et al, in press a), and a higher amount of dopaminergic D2 receptors in the striatum in comparison to the APO-UNSUS rats (Rots et al, 1996). Furthermore, the APO-SUS rats have a functionally lower noradrenergic activity in the ventral striatum than the APO-UNSUS rats as determined by (a-)adrenergic agents induced locomotor activity by accumbal infusions (Ellenbroek and Cools, 1993;Cools et al, 1990), and have lower plasma levels of free corticosterone (Rots et al, 1995).…”