H. Katagiri et al., Modulation of serotonin2A receptor function in rats after repeated treatment with dexamethasone and L-type calcium channel antagonist nimodipine, PROG NEUR-P, 25(6), 2001, pp. 1269-1281
Citations number
38
Categorie Soggetti
Neurosciences & Behavoir
Journal title
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
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.