Pretreatment with diazepam suppresses the reduction in defensive freezing behavior induced by fluvoxamine in the conditioned fear stress paradigm in mice.
The effects of the selective serotonin (5-hydroxytryptamine (5-HT)) reuptake inhibitor fluvoxamine, given alone or in combination with the benzodiazepine anxiolytic diazepam on the defensive freezing behavior of mice in the conditioned fear stress paradigm were examined. Fluvoxamine (5-20 mg/kg, i.p.) induced a dose-dependent reduction in freezing behavior. In contrast, while low doses of diazepam (0.125 and 0.25 mg/kg, i.p.) reduced the freezing behavior, such effects were not observed with high doses of diazepam (0.5 and 1 mg/kg, i.p.). In the combination study, fluvoxamine (20 mg/kg, i.p. ) did not reduce the freezing behavior in mice that had been pretreated with diazepam (0.125-1 mg/kg, i.p.). None of the doses of fluvoxamine and diazepam used in the present study had any effects on motor activity under non-stressed conditions. These results suggest that benzodiazepines may negatively influence the clinical efficacy of selective 5-HT reuptake inhibitors in the treatment of anxiety disorders.
Miyamoto
J
J
Department of Pharmacology and Intractable Disease Research Center, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, 160-8402, Tokyo, Japan.
Tsuji
M
M
Takeda
H
H
Nawa
H
H
Matsumiya
T
T
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology*; D005239:Fear / Q000523:psychology*; D016666:Fluvoxamine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D013315:Stress, Psychological / Q000523:psychology*
D014151:Anti-Anxiety Agents; D018687:Antidepressive Agents, Second-Generation; D016666:Fluvoxamine; D003975:Diazepam