Interaction of diazepam and swim stress.
Many people take diazepam to prevent or counteract the consequences of exposure to different stressors. However, the interaction of diazepam and stress is not clear. Several studies have suggested that swim stress alters the properties of benzodiazepines. Both diazepam and swim stress have anticonvulsant properties. To determine whether swim stress alters the activity of diazepam, we tested the anticonvulsant effect of diazepam given in combination with swim stress. The mice were, prior to exposure to swim stress (10 or 5 min swimming at ambient temperature) and the intravenous infusion of picrotoxin, pre-treated with diazepam or allopregnanolone, or 24 h after exposure to stress treated with diazepam. The latency to the onset of clonic and tonic seizures was registered and the threshold for picrotoxin-induced clonic and tonic seizures calculated. In swim stressed (10 min) mice diazepam (0.5 and 1.0 mg/kg) enhanced the threshold for picrotoxin-induced tonic seizures more than in unstressed mice. The effect of allopregnanolone (20 mg/kg) in combination with 10-min swim stress on the threshold for picrotoxin-induced tonic seizures was also supraadditive. When diazepam (1 mg/kg) was given 20 min prior to 5-min swim stress, or 24 h after 10-min swim stress, there was no significant change in its anticonvulsant activity between unstressed and swim stressed mice. The results demonstrate that the anticonvulsant and possibly other behavioral properties of diazepam given in combination with swim stress can be either potentiated or unchanged, depending on the duration of stress and the time of diazepam administration in relation to stress.
Pericić
Danka
D
Laboratory for Molecular Neuropharmacology, Division of Molecular Medicine, Ruder Bosković Institute, 10002, Zagreb, Croatia. pericic@irb.hr
Strac
Dubravka Svob
DS
Vlainić
Josipa
J
D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects; D003975:Diazepam / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D051379:Mice; D010852:Picrotoxin; D011280:Pregnanolone / Q000008:administration & dosage; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology*; D013315:Stress, Psychological / Q000209:etiology / Q000503:physiopathology*; D013550:Swimming / Q000523:psychology
D000927:Anticonvulsants; D003975:Diazepam; D004338:Drug Combinations; D010852:Picrotoxin; D011280:Pregnanolone