Effects of swim stress and alpha-MSH acute pre-treatment on brain 5-HT transporter and corticosterone receptor

The forced swim test (FST) can lead to stress-related diseases such as depression, through activation of hypothalamic-pituitary-adrenal axis (HPAA) and corticosteroid disregulation. Among the proopiomelanocortin (POMC)-derived peptides, alpha-melanocyte-stimulating hormone (alpha-MSH) has been shown to regulate long-lasting behavioral responses. Moreover, serotonergic pathways in various brain areas are activated by stressors, a feature that suggests a role for serotonin in both stress-induced HPAA disregulation and depressive physiopathology. Taking all together these data, we investigated the effects of the FST exposure and the effects of pre-treatment with alpha-MSH on cortical synaptosomal serotonin transporter (SERT) activity, corticosterone (CORT) plasma levels and on glucocorticoid receptor (GR) occupancy and expression in rat hippocampus. Young male rats were divided into three groups treated with saline or with alpha-MSH at doses of 1 or 4 microg/rat, 15 min prior to FST. Our data show that FST increased CORT secretion; GR levels in hippocampus decreased in density after stress without variations in affinity; GR redistributed from the cytosolic to the nuclear tissue fraction; finally, SERT activity strongly increased. All these effects were blocked by pre-treatment with alpha-MSH at the higher dose.