Monoamine receptors in the prefrontal cortex of Tupaia belangeri during chronic psychosocial stress.

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.