title: Influence of diltiazem on the behavior of zolpidem-treated mice in the elevated-plus maze test.
abstract: The present study was undertaken to investigate the effect of diltiazem, a L-type calcium channel blocker (CCB), on the behavior of zolpidem-treated mice in the elevated plus-maze (EPM). Atypical benzodiazepine zolpidem significantly increased the percentage of open arm entries without influencing the total entries and total distance and average speed at the dose of 5 mg/kg (p.o.). Co-administration of zolpidem (2 mg/kg, p.o.) and diltiazem (5, 10 and 20 mg/kg, p.o.) significantly increased both the time spent and arm entries in the open arms without influencing the total entries and spontaneous activity notwithstanding that zolpidem at dose up to 2 mg/kg (p.o.) and diltiazem at dose up to 20 mg/kg (p.o.) did not show any effects on mice behavior in EPM. Zolpidem also attenuated the anxiogenic effect of 1-(3-Chlorophenyl)piperazine (mCPP, 0.7 mg/kg, i.p.) and 5-hydroxytryptophan (5-HTP, 30 mg/kg, i.p.). Even though the zolpidem at 1 mg/kg and diltiazem at 5 mg/kg were ineffective on mCPP-induced anxiety, respectively, the co-administration of zolpidem (1 mg/kg, i.p.) and diltiazem (5 mg/kg, p.o.) showed inhibitory effect on mCPP-induced anxiety in mice. These results suggested that diltiazem, a L-type CCB may augment the anxiolytic-like effect of zolpidem and also indicated that calcium channel modulation maybe involved in the anxiolytic-like properties of zolpidem.
authors.affiliation: Department of Pharmacology, School of Basic Medical Science, Peking University, Beijing, China.
authors.forename: X-Y
authors.initials: XY
authors.lastname: Cui
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: Q-P
authors.initials: QP
authors.lastname: Chu
authors.forename: B-Q
authors.initials: BQ
authors.lastname: Chen
authors.forename: Y-H
authors.initials: YH
authors.lastname: Zhang
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy*; D001569:Benzodiazepines / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology*; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D000077334:Zolpidem
chemical_list: D014151:Anti-Anxiety Agents; D002121:Calcium Channel Blockers; D018755:GABA Agonists; D010879:Piperazines; D011725:Pyridines; D017366:Serotonin Receptor Agonists; D001569:Benzodiazepines; D000077334:Zolpidem; D006916:5-Hydroxytryptophan; D004110:Diltiazem; C015068:1-(3-chlorophenyl)piperazine