Chronic administration of citalopram increased L-type VDCC current. (a) Outline of recordings from citalopram-administrated mice. After chronic treatment with citalopram (Cit; 24 mg/kg/day) or its vehicle (Water) for 28 days, acute raphe slices were prepared, and whole-cell voltage clamp recordings were performed. (b) Representative traces (left) and peak current (right) of high voltage activated (HVA) current in DRN serotonergic neurons from drug-naïve (Water) and citalopram-treated (Cit) mice. *P < 0.05 vs. Water. (Water, n = 8 neurons from 3 mice; Cit, n = 9 neurons from 4 mice; Student’s t-test; P = 0.0487). (c) Effects of intracellularly applied D890 on HVA current in DRN serotonergic neurons. P = 0.3402 vs. Water by Student’s t-test, Water, n = 8 neurons from 2 mice; Cit, n = 8 neurons from 2 mice. (d) Effects of bath-applied CGP52432 on high voltage activated (HVA) current in DRN serotonergic neurons. P = 0.5283 vs. Water by Student’s t-test, Water, n = 14 neurons from 4 mice; Cit, n = 11 neurons from 2 mice. (e) HVA VDCC current was recorded in the presence of WAY100635 and GR127935. *P < 0.05 vs. Water. (Water, n = 11 neurons from 2 mice; Cit, n = 12 neurons from 2 mice; Student’s t-test; P = 0.0107). (f) Effects of intracellularly applied KT5720 on HVA current in DRN serotonergic neurons. P = 0.6866 vs. Water by Student’s t-test, Water, n = 10 neurons from 2 mice; Cit, n = 12 neurons from 2 mice. (g) Effects of intracellularly applied gallein (20 μM) on HVA current in DRN serotonergic neurons. *P < 0.05 vs. Water. (Water, n = 12 neurons from 2 mice; Cit, n = 17 neurons from 2 mice; Student’s t-test; P = 0.0172). Data are presented as the mean ± S.E.M. (h) In normal condition, continuous GABAB receptor signaling inhibits PKA activation. Decreased PKA activity might cause inhibition of L-type VDCC activity and subsequently serotonergic firing activity. After chronic antidepressant treatment, postsynaptic GABAB signaling is decreased, resulting in activation of PKA and disinhibition of L-type VDCCs. Increasing Ca2+ current through L-type VDCCs accelerates serotonergic firing activity.