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β-Adrenoceptors in the Tree Shrew Brain. II. Time-Dependent Effects of Chronic Psychosocial Stress on [125I]Iodocyanopindolol Binding Sites

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Abstract

1. Stress is known to affect the functioning of the central noradrenergic system in a region-specific manner. The aim of the present investigation was to understand better the consequences of recurrent stressful experiences on central β-adrenoceptors.

2. Alterations in the central nervous β-adrenoceptor system resulting from different periods of psychosocial stress (PSS) were analyzed in male tree shrews (Tupaia belangeri) which were submitted to subordination stress for varying time periods.

3. In the first experiment, the whole number of β-adrenoceptors was analyzed in the forebrains of subordinate animals and controls by in vitro autoradiography using 125I-iodocyanopindolol (125ICYP), while nonspecific binding of the radioligand to serotonin receptors was blocked with 100 μM 5HT.

4. PSS affects β-adrenoceptors in a time-dependent manner. A decrease in receptor affinity occurred after just 21 days of PSS in cortical areas and in the hippocampus, indicating stress effects on the conformation of β-adrenoceptors. After 30 days of PSS,the numbers of β-adrenoceptors were significantly decreased in several cortical regions and in the olfactory area.

5. In the second experiment, we investigated the influence of PSS on both β1- and β2-adrenoceptors separately. 125ICYP binding was quantified in the presence of either ICI188.551 to block β2-adrenoceptors or in the presence of CGP20712A to block β1-adrenoceptors.

6. After 2, 10, 21,and 28 days of PSS, it become apparent that the two β-adrenoceptor subtypes are regulated independently. β1-Adrenoceptors were transiently down-regulated after 2 days of PSS in the prefrontal cortex and in the olfactory area and were decreased after 28 days of PSS in the parietal cortex and the hippocampus. A transient up-regulation of β1-adrenoceptors occurred in the pulvinar nucleus after 10 days of PSS. β2-Adrenoceptors were transiently down-regulated after 2 days of PSS in the prefrontal cortex and up-regulated in the pulvinar nucleus after 28 days of PSS.

7. These data demonstrate that chronic psychosocial stress in subordinate tree shrews leads to time-dependent changes in the central nervous β-adrenoceptors system.

8. The high regional variability in stress-induced β-adrenoceptor regulation is supposed to be due to the complex mechanisms of intracellular β-adrenoceptor sequestration, which includes down-regulation and/or reinsertion of receptors into the plasma membrane. These mechanisms may be important components of the regulatory apparatus which enables the individual to adapt to situations of recurrent stressful experiences by balancing the central nervous adrenoceptor number.

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Flügge, G., Ahrens, O. & Fuchs, E. β-Adrenoceptors in the Tree Shrew Brain. II. Time-Dependent Effects of Chronic Psychosocial Stress on [125I]Iodocyanopindolol Binding Sites. Cell Mol Neurobiol 17, 417–432 (1997). https://doi.org/10.1023/A:1026387311220

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