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Monoamine receptors in the prefrontal cortex of Tupaia belangeri during chronic psychosocial stress (1997)

Flügge, G. ; Ahrens, O. ; Fuchs, E.

Springer

Cell & tissue research 288 (1997), S. 1-10

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ISSN: 1432-0878

Keywords: Key words: Alpha2-adrenoceptor ; Beta-adrenoceptor ; 5HT1A receptor ; Stress ; Desensitisation ; Tree shrew ; Tupaia belangeri (Scandentia)

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Medicine

Notes: Abstract. The prefrontal cortex has been reported to be involved in the regulation of emotional behaviour by integrating cognitive, emotional and autonomic information processes, and impairments of its functions are implicated in psychopathologies such as depression. Neuronal functioning in the prefrontal cortex is under the control of the noradrenergic and the serotonergic system which are both activated during stress. The present study aimed to quantify the effect of chronic psychosocial stress on alpha2-adrenoceptors, beta-adrenoceptors, and serotonin1A receptors in the prefrontal cortex. Male tree shrews (Tupaia belangeri) were subjected to subordination stress for 2, 10, 21 and 28 days, and binding sites for the alpha2-adrenergic antagonists 3H-rauwolscine and 3H-RX821002, for the beta-adrenergic antagonist 125I-iodocyanopindolol, and for the 5-hydroxytryptamine (5HT)1A receptor agonist 3H-8-hydroxy-2-(di-n-propylamino)tetralin were quantified by in vitro receptor autoradiography. Chronic psychosocial stress induced time-dependent receptor down- and upregulations. Beta-adrenoceptors were transiently reduced in numbers after just 2 days of psychosocial stress which is interpreted as agonist-mediated downregulation induced by high local concentrations of noradrenaline released from terminals originating from the locus coeruleus. Alpha2-adrenoceptors were transiently downregulated after 10 days, and upregulated after 28 days of psychosocial stress. These data indicate that the noradrenergic system adapts to the stress by counterbalancing its receptor numbers. 5HT1A receptors were only downregulated after 28 days of psychosocial stress, and thus react later than the noradrenergic receptors. In summary, our results show that monoaminergic receptors in the prefrontal cortex of tree shrews undergo dynamic changes during chronic psychosocial stress. These alterations probably have an impact on neuronal activity, and might contribute to the behavioural changes which have been previously described in subordinate male tree shrews.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/s004410050787

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β-Adrenoceptors in the Tree Shrew Brain. II. Time-Dependent Effects of Chronic Psychosocial Stress on [125I]Iodocyanopindolol Binding Sites (1997)

Flügge, G. ; Ahrens, O. ; Fuchs, E.

Springer

Cellular and molecular neurobiology 17 (1997), S. 417-432

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ISSN: 1573-6830

Keywords: β-adrenoceptors ; down-regulation ; stress ; depression ; tree shrew

Source: Springer Online Journal Archives 1860-2000

Topics: Biology

Notes: 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.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1026387311220

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β-Adrenoceptors in the Tree Shrew Brain. I. Distribution and Characterization of [125I]Iodocyanopindolol Binding Sites (1997)

Flügge, G. ; Ahrens, O. ; Fuchs, E.

Springer

Cellular and molecular neurobiology 17 (1997), S. 401-415

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ISSN: 1573-6830

Keywords: β-adrenoceptor ; 125I-cyanopindolol ; sequestration ; down-regulation ; CGP20712A ; ICI118.551

Source: Springer Online Journal Archives 1860-2000

Topics: Biology

Notes: Abstract 1. The number and distribution pattern of β-adrenergic receptors in the brain have been reported to be species specific. The aim of the present study was to describe binding of the β-adrenoceptor ligand [125I]iodocyanopindolol in the brain of the tree shrew (Tupaia belangeri), a species which provides an appropriate model for studies of psychosocial stress and its consequences on central nervous processes. 2. 125I-Iodocyanopindolol (125ICYP) labeling revealed a high degree of nonspecific binding, which was due mainly to interactions of this ligand with serotonin binding sites. For a quantitative evaluation of β1- and β2-adrenoceptors, serotonin binding sites had to be blocked by 100 μM 5HT. 3. Binding of the radioligand to β1- and β2-adrenoceptors was characterized using the β1-specific antagonist CGP20712A and the β2-specific antagonist ICI118.551. β1-adrenoceptor binding is present in the whole brain, revealing low receptor numbers in most brain regions (up to 1.5 to 2.7 fmol/mg). A slight enrichment was observed in cortical areas (lateral orbital cortex: 4.0±0.7 fmol/mg) and in the cerebellar molecular layer (8.7±1.0 fmol/mg). 4. Competition experiments demonstrated high- and low-affinity binding sites with considerable variations in K i values for CGP20712A, showing that various affinity states of β1-adrenoceptors are present in the brain (K i: 0.61 nM to 67.1 μM). In the hippocampus, only low-affinity β1-adrenoceptors were detected (K i: 1.3±0.2 μM). Since it is known that 125ICYP labels not only membrane bound but also internalized β-adrenoceptors, it can be assumed that the large population of the low-affinity sites represents internalized receptors which may be abundant due to a high sequestration rate. 5. High numbers of β2-adrenoceptors are present in only a few brain structures of tree shrews (external layer of the olfactory bulb, 15.8±2.0 fmol/mg; claustrum, 19.3±1.5 fmol/mg; anteroventral thalamic nucleus, 19.4±1.5 fmol/mg; cerebellar molecular layer, 55.0±4.3 fmol/mg). Also for this class of β-adrenoceptors, high- and low-affinity binding sites for the β2-selective antagonist ICI118.551 were observed, indicating that 125ICYP labels membrane bound and internalized β2-adrenoceptors. Only in the cerebellar molecular layer was a high percentage of high-affinity β2-adrenoceptors detected (K i for ICI118.551 was 1.8±0.3 nM for 90% of the receptors). 6. In conclusion, β1- and β2-adrenoceptor binding can be localized and quantified by in vitro receptor autoradiography in the brains of tree shrews when serotonergic binding sites are blocked. Modulatory effects of long-term psychosocial conflict on the central nervous β-adrenoceptor system in male tree shrews are described in the following paper.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1026335327150

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