Modulation of serotonin2A receptor function in rats after repeated treatment with dexamethasone and L-type calcium channel antagonist nimodipine

1. It has been conceivable that the hypo thalamic-pituitary-adrenal (HPA) a xis hyperactivity plays an important role in the pathophysiology of depress ion. In the present study, we have investigated the effect of repeated trea tment with dexamethasone on serotonin (5-HT) 1A, 5-HT2A and al-adrenergic r eceptors in the rat frontal cortex. Moreover, several studies have suggeste d the effectiveness of L-type calcium channel antagonist nimodipine for the treatment of depression. We also investigated the effect of repeated treat ment with nimodipine on 5-HT2A receptor in rats with repeated dexamethasone treatment. 2. Repeated treatment with dexamethasone (1 mg/kg/day for 14 days) increase d the density of 5-HT2A receptor, but not 5-HT1A and al-adrenergic receptor s in the rat frontal cortex. 3. The density of 5-HT2A receptor in the rat frontal cortex was significant ly increased 1 day after repeated treatment with dexamethasone, but was not increased 7 or 14 days after repeated treatment. Wet dog shakes (WDS) indu ced by (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (D OI), a 5-HT2A receptor agonist, in rats were significantly enhanced 1, 7 an d 14 days after repeated treatment with dexamethasone, although the frequen cy of WDS gradually decreased after repeated treatment. 4. Repeated treatment with nimodipine (5 mg/kg/day for 14 days) attenuated DOI-induced WDS enhanced by repeated treatment with dexamethasone (1 mg/kg/ day for 14 days), however, it did not change the density of 5-HT2A receptor . Repeated treatment with dexamethasone decreased locomotor activity and bo dy weight, but repeated treatment with nimodipine did not recover these par ameters. 5. The results of the present study suggest that repeated treatment with de xamethasone may selectively increase the 5-HT2A receptor in the rat frontal cortex and affect 5-HT2A receptor-mediated signal transduction. In additio n, the intracellular calcium homeostasis by blocking calcium influx through L-type calcium channel may play an important role in the regulation of the 5-HT2A receptor function by dexamethasone.