Adrenalectomy modifies the hippocampal 5-HT_1A receptors and the anxiolytic-like effect of 8-OH-DPAT in rats

Stress is closely related with levels of corticosteroid and corticotrophin releasing factor, which at the same time can modify 5-HT_1A receptors and brain serotonin levels. Consequently, the absence of corticosteroids in rats induced by an adrenalectomy could be useful to understand the functionality of the brain serotonergic system after a stressing event. The influence of 15 min of forced swimming was explored on sham and adrenalectomized rats by measuring the 5-HT_1A receptor density in raphe and hippocampus. Other previously stressed groups (sham and adrenalectomized) were tested in two anxiety models with the 5-HT_1A agonist 8-OH-DPAT, the postsynaptic antagonist MM-77, and with a combination of these two compounds. It was found that the removal of adrenals in rats that were not previously stressed induced an increase in the postsynaptic 5-HT_1A receptor density. On the other hand, an adrenalectomy in rats that were previously stressed induced a reduction in the same receptor density. Adrenal gland removal induced an anxiolytic-like effect. However, after the injection of 8-OH-DPAT, adrenalectomized rats showed anxiogenic-like actions, an effect which was reversed by MM-77. Data show that changes in 5-HT_1A receptors density caused by a stressful session can have behavioral consequences, thus emphasizing the need to reconsider the clinical use of 5-HT_1A ligands after traumatic events.