| dc.description | Modifications produced at lymphocyte serotonergic system could be associated to
immune alterations observed in chronic stressed rats and depressive patients. The
dysregulation of the hypothalamic-pituitary-adrenal axis and the increase of blood
glucocorticoid levels reported in these patients might be involved in such changes.
To investigate the effects of stress on some functional aspects of serotonin
transporter (5-HTT) from rat lymphocytes we applied two stress models to adult
male rats: 1) physical restraint stress 5 hours/day for 5 days or 2) intraperitoneal
injection of 2,5 mg/kg/day of reserpine for 3 days with the aims to: a) measure the
proliferative response of lymphocytes to the mitogen concanavalin A (Con A) in
the presence or in the absence of fluoxetine and b) calculate affinity constants
(Kd), number of binding sites (Bmax) and Hill coefficients (nH) from [3H]-
paroxetine binding using lymphocytes membranes. Morning serum corticosterone
concentration was measured with an EIA kit of DSL. Corticosterone values in
restrained: 544±52 ng/ml and controls: 232±74 ng/ml (p<0.05), reserpine treated:
467±94 ng/ml and controls: 322±39 ng/ml. Lymphocytes were isolated by Ficoll-
Hypaque density gradients and differential adhesion to plastic. Cell proliferation
was measured with a tetrazolium salt. In the restraint stress group, fluoxetine
reduced basal proliferation at 5 μM in controls and at 25 μM in restrained. In the
presence of Con A, fluoxetine had an antiproliferative effect at 5 μM in controls
and at 10 μM in restrained. In the reserpine treated group, fluoxetine had a basal
antiproliferative effect at 5 μM in controls and in treated rats. In the presence of
Con A, fluoxetine had an antiproliferative effect at 5 μM in controls and at 10 μM
in treated rats. In both stress groups it was observed a significant increase in
Bmax, Kd and nH respect to controls. These parameters changes indicate an
elevation of the number of binding sites with a concomitant decrease in the
affinity for the ligand and a loss of cooperativity for the binding to 5-HTT of
lymphocytes from stressed rats, and are probably related to the differential
sensitivity to fluoxetine observed in culture assays. Glucocorticoids might be
involved in these alterations, although other unknown mechanisms could
participate either. | |
