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Corticosteroid feedback resistance in rats genetically selected for increased dopamine responsiveness
N Y Rots1, A R Cools, J de Jong
1Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, University of Leiden, The Netherlands.
Journal of Neuroendocrinology
|February 1, 1995
Summary
Apomorphine-susceptible rats exhibit heightened hypothalamus-pituitary-adrenal (HPA) axis activity and stress responses compared to unsusceptible rats, indicating a link between dopamine system responsiveness and HPA axis function.
Area of Science:
- Neuroendocrinology
- Behavioral Neuroscience
Background:
- The hypothalamus-pituitary-adrenal (HPA) axis is the primary stress response system.
- Dopamine system activity influences various physiological processes, including stress regulation.
Purpose of the Study:
- To investigate the relationship between dopamine system responsiveness and HPA axis activity.
- To characterize stress responses in Wistar rat lines with differing dopamine system sensitivities.
Main Methods:
- Pharmacogenetic selection of Wistar rats based on apomorphine-induced gnawing response (apo-sus vs. apo-unsus).
- Measurement of HPA axis hormones (CRH, ACTH, corticosterone) under basal and stress conditions (novel environment, CRH stimulation).
- In vitro assessment of adrenocortical cell responsiveness to ACTH.
Main Results:
- Apomorphine-susceptible (apo-sus) rats displayed higher basal CRH mRNA and ACTH levels, with lower free corticosterone.
- Apo-sus rats showed exaggerated and prolonged ACTH and corticosterone responses to novelty stress.
- Enhanced pituitary ACTH and corticosterone release in apo-sus rats upon CRH stimulation, with higher in vitro adrenal responsiveness to ACTH.
Conclusions:
- Dopamine system responsiveness significantly modulates HPA axis activity and stress reactivity.
- Higher dopamine system responsiveness is associated with an overactive HPA axis and exaggerated stress responses.