A single inescapable shock (IS) session induced long-term behavioral deficits, persistently elevated corticosterone
levels and changes in central glucocorticoid receptors (GR), a system involved in the etiology of affective disorders.Antidepressants (AD) with different mechanisms of action (tricyclics, SSRIs) affected the changes on GR after IS in diverse brain areas in a time- and compound-dependent manner. Only desipramine (DMI), a tricyclic, when administered chronically was effective to reverse the behavioral alterations induced by IS and concomitantly normalize corticosterone secretion pattern. Central corticosteroid receptor systems?MR and GR?appear to be critical for glucocorticoids? control over the HPA
axis activity and for behavioral impairment elicited by stress. This work aimed to study the temporal course of IS effects on MR and their modulation by AD, both in relation to HPA activity. DMI or fluoxetine (10
mg/kg i.p.), were each administered 3 and 6 days following IS. MR occupancy was estimated measuring available cytosolic receptors in intact rats and total receptors in adrenalectomized animals. IS led to a long-term increase in MR occupancy in the hippocampus compared to nonstressed animals. Both AD treatments restored MR occupancy to control levels. In frontal cortex, IS-induced changes on MR were not affected by AD, whereas no differences were found in amygdala and hypothalamus. The AD effectiveness to restore MR balance and basal corticosterone levels highlights hippocampal MR involvement in the maintenance of endocrine homeostasis. In this rodent model,MR(in concert with GR) are critically involved in cognitive aspects and termination of the stress response.
levels and changes in central glucocorticoid receptors (GR), a system involved in the etiology of
affective disorders.Antidepressants (AD) with different mechanisms of action (tricyclics, SSRIs) affected
the changes on GR after IS in diverse brain areas in a time- and compound-dependent manner. Only
desipramine (DMI), a tricyclic, when administered chronically was effective to reverse the behavioral
alterations induced by IS and concomitantly normalize corticosterone secretion pattern. Central corticosteroid
receptor systems?MR and GR?appear to be critical for glucocorticoids? control over the HPA
axis activity and for behavioral impairment elicited by stress. This work aimed to study the temporal course of IS effects on MR and their modulation by AD, both in relation to HPA activity. DMI or fluoxetine (10
mg/kg i.p.), were each administered 3 and 6 days following IS. MR occupancy was estimated measuring available cytosolic receptors in intact rats and total receptors in adrenalectomized animals. IS led to a long-term increase in MR occupancy in the hippocampus compared to nonstressed animals. Both AD treatments restored MR occupancy to control levels. In frontal cortex, IS-induced changes on MR were not affected by AD, whereas no differences were found in amygdala and hypothalamus. The AD effectiveness to restore MR balance and basal corticosterone levels highlights hippocampal MR involvement in the maintenance of endocrine homeostasis. In this rodent model,MR(in concert with GR) are critically involved in cognitive aspects and termination of the stress response.
axis activity and for behavioral impairment elicited by stress. This work aimed to study the temporal course
of IS effects on MR and their modulation by AD, both in relation to HPA activity. DMI or fluoxetine (10
mg/kg i.p.), were each administered 3 and 6 days following IS. MR occupancy was estimated measuring available cytosolic receptors in intact rats and total receptors in adrenalectomized animals. IS led to a long-term increase in MR occupancy in the hippocampus compared to nonstressed animals. Both AD treatments restored MR occupancy to control levels. In frontal cortex, IS-induced changes on MR were not affected by AD, whereas no differences were found in amygdala and hypothalamus. The AD effectiveness to restore MR balance and basal corticosterone levels highlights hippocampal MR involvement in the maintenance of endocrine homeostasis. In this rodent model,MR(in concert with GR) are critically involved in cognitive aspects and termination of the stress response.
mg/kg i.p.), were each administered 3 and 6 days following IS. MR occupancy was estimated measuring
available cytosolic receptors in intact rats and total receptors in adrenalectomized animals. IS led to a
long-term increase in MR occupancy in the hippocampus compared to nonstressed animals. Both AD
treatments restored MR occupancy to control levels. In frontal cortex, IS-induced changes on MR were
not affected by AD, whereas no differences were found in amygdala and hypothalamus. The AD effectiveness
to restore MR balance and basal corticosterone levels highlights hippocampal MR involvement
in the maintenance of endocrine homeostasis. In this rodent model,MR(in concert with GR) are critically
involved in cognitive aspects and termination of the stress response.
