BETA-ADRENOCEPTORS IN THE TREE SHREW BRAIN .2. TIME-DEPENDENT EFFECTSOF CHRONIC PSYCHOSOCIAL STRESS ON [I-125] IODOCYANOPINDOLOL BINDING-SITES

1. Stress is known to affect the functioning of the central noradrener gic system in a region-specific manner, The aim of the present investi gation was to understand better the consequences of recurrent stressfu l experiences on central beta-adrenoceptors. 2. Alterations in the cen tral nervous beta-adrenoceptor system resulting from different periods of psychosocial stress (PSS) were analyzed in male tree shrews (Tupai a belangeri) which were submitted to subordination stress for varying time periods, 3. In the first experiment, the whole number of beta-adr enoceptors was analyzed in the forebrains of subordinate animals and c ontrols by in vitro autoradiography using I-125-iodocyanopindolol ((IC YP)-I-125), while nonspecific binding of the radioligand to serotonin receptors was blocked with 100 mu M 5HT. 4. PSS affects beta-adrenocep tors in a time-dependent manner, A decrease in receptor affinity occur red after just 21 days of PSS in cortical areas and in the hippocampus , indicating stress effects on the conformation of beta-adrenoceptors. After 30 days of PSS, the numbers of beta-adrenoceptors were signific antly decreased in several cortical regions and in the olfactory area, 5. In the second experiment, we investigated the influence of PSS on both beta(1)- and beta(2)-adrenoceptors separately, (ICYP)-I-125 bindi ng was quantified in the presence of either ICI188.551 to block beta(2 )-adrenoceptors or in the presence of CGP20712A to block beta(1)-adren oceptors. 6. After 2, 10, 21, and 28 days of PSS, it become apparent t hat the two beta-adrenoceptor subtypes are regulated independently. be ta(1)-Adrenoceptors were transiently down-regulated after 2 days of PS S in the prefrontal cortex and in the olfactory area and were decrease d after 28 days of PSS in the parietal cortex and the hippocampus. A t ransient up-regulation of beta(1)-adrenoceptors occurred in the pulvin ar nucleus after 10 days of PSS. beta(2)-Adrenoceptors were transientl y down-regulated after 2 days of PSS in the prefrontal cortex and up-r egulated in the pulvinar nucleus after 28 days of PSS. 7. These data d emonstrate that chronic psychosocial stress in subordinate tree shrews leads to time-dependent changes in the central nervous beta-adrenocep tors system. 8. The high regional variability in stress-induced beta-a drenoceptor regulation is supposed to be due to the complex mechanisms of intracellular beta-adrenoceptor sequestration, which includes down -regulation and/or reinsertion of receptors into the plasma membrane. These mechanisms may be important components of the regulatory apparat us which enables the individual to adapt to situations of recurrent st ressful experiences by balancing the central nervous adrenoceptor numb er.