Rats bred for enhanced apomorphine susceptibility have elevated tyrosine hydroxylase mRNA and dopamine D2-receptor binding sites in nigrostriatal and tuberoinfundibular dopamine systems

Rots, Nynke Y.; Cools, Alexander R.; Bérod, Anne; Voorn, Pieter; Rostène, William; Kloet, E. Ronald de

doi:10.1016/0006-8993(95)01379-2

Cited by 48 publications

(28 citation statements)

References 26 publications

(17 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Genetically determined differences in dopaminergic activity have also been connected to differences in behavior and altered HPA-axis activity in rats [Cools et al, 1990[Cools et al, , 1995[Cools et al, , 1996a. Using a selection model based on the extent of stereotypic gnawing elicited by the dopamine D1/D2 receptor agonist apomorphine Cools et al [1990], found that high susceptibility to apomorphine-induced stereotypic behavior co-occured with increased locomotor activity in a novel environment.…”

Section: Discussionmentioning

confidence: 99%

Brain Monoaminergic Activity in Rainbow Trout Selected for High and Low Stress Responsiveness

Øverli

Pottinger²,

Carrick³

et al. 2001

Brain Behav Evol

168

118

View full text Add to dashboard Cite

This paper investigates whether two lines of rainbow trout displaying genetically determined variation in stress responsiveness and behavior also show differences in brain monoaminergic activity. In several brain regions, strains of rainbow trout selected for consistently high or low post-stress cortisol levels displayed differences in tissue concentrations of monoamines and/or monoamine metabolites, or in metabolite/monoamine ratios. High-responsive trout reacted to stress by an increase in the concentrations of both serotonin (brain stem), dopamine (brain stem), and norepinephrine (optic tectum, telencephalon), whereas low-responsive fish did not. Brain stem and optic tectum concentrations of monoamine metabolites were also elevated after stress in high responders, but not in low-responsive fish. The simultaneous increase in the concentration of monoamines and their metabolites suggests that both synthesis and metabolism of these transmitters were elevated after stress in high-responsive trout. A divergent pattern was seen in the hypothalamus, where low-responsive fish displayed elevated levels of 5-hydroxyindoleacetic acid (a serotonin metabolite) and 3-methoxy-4-hydroxyphenylglycol (a norepinephrine metabolite). In the telencephalon, both populations had elevated concentrations of these metabolites after stress. These results clearly suggest that selection for stress responsiveness in rainbow trout is also associated with changes in the function of brain monoaminergic systems. The possible functional significance of these observations is discussed with respect to the physiological and behavioral profile of these strains of fish. Literature is reviewed showing that several factors affecting brain monoaminergic activity might be altered by selection for stress responsiveness, or alternatively be under direct influence of circulating glucocorticoids.

show abstract

Section: Discussionmentioning

confidence: 99%

Brain Monoaminergic Activity in Rainbow Trout Selected for High and Low Stress Responsiveness

Øverli

Pottinger²,

Carrick³

et al. 2001

Brain Behav Evol

168

118

View full text Add to dashboard Cite

show abstract

“…This finding is of interest, since these indices of dopamine responsiveness show a profound line difference at adult hood. In a previous study we observed that 2-month-old apo-sus rats have higher levels of D1 receptor mRNA and D2 receptor binding as well as TH mRNA expression in the nigrostriatal and tubero-infundibular pathway, but not in the mesolimbic dopamine projections [17]. Apparently, the divergence in dopamine responsiveness shows some selectivity for the nigrostriatal and tuberoinfundibular sys tems and it develops post-weaning.…”

Section: Discussionmentioning

confidence: 81%

“…We found no divergence in the dopamine systems of rats of the two selection lines around the age of weaning the dopamine system to apomorphine we have previously when the line differences in HPA activity have already quantified several parameters indicative of the activity of developed. this system [17]. Adult apo-sus rats showed a significantly elevated tyrosine hydroxylase mRNA expression in neu rons of the A9 nigrostriatal and A12 tuberoinfundibular dopamine system.…”

Section: N Y Rots Et Al / Developmental Brain Research 92 (¡996) 1mentioning

confidence: 95%

See 1 more Smart Citation

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

Rots

Workel²,

Oitzl³

et al. 1996

Developmental Brain Research

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Moreover, the apo-sus animals showed significantly more [125Iliodosulpiride binding to D2 receptors in the striatum, but not in the nucleus accumbens, of the apo-sus animals (22). Thus, selection for apomorphine susceptibility is related to altered dopaminergic function in the tuberoinfundibular and nigrostriatal pathways.…”

Section: Discussionmentioning

confidence: 94%

Divergent prolactin and pituitary-adrenal activity in rats selectively bred for different dopamine responsiveness.

Rots¹,

Cools²,

Oitzl³

et al. 1996

Endocrinology

View full text Add to dashboard Cite

The present study explores the significance of brain dopamine phenotype for individual variation in the neuroendocrine stress re sponse of the rat. For this purpose, we used two W istar ra t lines previously selected for high or low responsiveness of the dopamine system to apomorphine using the gnawing response as the selection criterion, Systemic administration of the drug evoked in apomorphine-susceptible (apo-sus) rats a vigorous gnawing response, whereas apomorphine-unsusceptible (apo-unsus) rats did not gnaw under these conditions. These two rat lines represent individuals displaying extreme differences in gnawing behavior th at otherwise coexist in a normal Wistar population. In this study basal and stressinduced hypothalamic-pituitary-adrenal activity and PRL release were m easured in chronically cannulated, freely moving rats that endured a conditioned emotional response. Tyrosine hydroxylase messenger RNA (mRNA), corticosteroid receptor mRNA, and in vivo retention of [3H]corticosterone were measured in ra t brain sections using in situ hybridization and in vivo autoradiography.The results show th at 1) apo-sus rats had a markedly reduced PRL response to stress compared to apo-unsus animals, whereas basal levels were not significantly different. A12 dopaminergic neurons in the arcuate nucleus expressed significantly higher levels of tyrosine hydroxylase mRNA in apo-sus rats, suggesting th at the reduced stress-induced PRL release could be due to an increased inhibitory R ECENT STUDIES have shown that dopamine is linked to stress. For instance, stress induces a PRL response, and this release of PRL is under inhibitory control of dopa mine (1-3). Furthermore, rats with a predisposition to de velop amphetamine self-administration display prolonged adrenocortical activation and increased locomotor activity after exposure to the stress of novel environment (4-6). Glu cocorticoids promote activation and sensitization of the as cending dopaminergic neurons. Moreover, dopaminergic ac tivation of CRH neurons may occur (7,8). The data add to a growing body of evidence suggesting adverse effects of ab errant corticosteroid hormone signaling on dopaminedependent psychopathology; including psychoses precipi tated by excess glucocorticoids and stress. The susceptibility control by dopaminergic neurons; 2) in apo-sus rats, stress resulted in a sustained elevation of ACTH and free corticosterone levels, whereas the total corticosterone levels were not different between the two ra t lines; 3) under basal morning conditions, apo-sus ra ts had significantly higher plasm a ACTH, but, in contrast, lower free cor ticosterone than apo-unsus rats; total plasm a corticosterone levels were not different; 4) the basal evening ACTH level was elevated in apo-sus rats; after removal of the adrenals in the morning, this in creased ACTH level in apo-sus rats persisted into the afternoon 6 h postadrenalectomy; and 5) hippocampal mineralocorticoid (MR), but not glucocorticoid (GR), receptor capacity w as increased in apo-sus rats...

show abstract

Rats bred for enhanced apomorphine susceptibility have elevated tyrosine hydroxylase mRNA and dopamine D2-receptor binding sites in nigrostriatal and tuberoinfundibular dopamine systems

Cited by 48 publications

References 26 publications

Brain Monoaminergic Activity in Rainbow Trout Selected for High and Low Stress Responsiveness

Brain Monoaminergic Activity in Rainbow Trout Selected for High and Low Stress Responsiveness

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

Divergent prolactin and pituitary-adrenal activity in rats selectively bred for different dopamine responsiveness.

Contact Info

Product

Resources

About