The modified light/dark transition test in mice: evaluation of classic and putative anxiolytic and anxiogenic drugs.
1. We devised a new light/dark transition apparatus, recorded transitions, % time animals spent outside the dark chambers (% time) and locomotor activity, and evaluated this apparatus by testing anxiolytics, non-anxiolytic drugs and putative anxiogenic drugs in mice. 2. Diazepam and alprazolam significantly increased transitions, % time and locomotor activity. The effects of 1 mg/kg (i.p.) diazepam on these parameters in this modified test were blocked by flumazenil, a selective benzodiazepine antagonist. 3. Anxiogenic drugs such as beta-carboline-3-carboxylic acid ethyl ester (beta-CCE) and picrotoxin significantly decreased all three parameters. Another anxiogenic drug, yohimbine, also significantly decreased transitions and locomotor activity, but it significantly increased % time at 5 mg/kg (i.p.). 4. Imipramine (5-10 mg/kg, i.p.), an antidepressant, sulpiride (10-25 mg/kg, i.p.), an antipsychotic drug, and scopolamine (0.1-1 mg/kg, i.p.), an anticholinergic drug, had no effect. 5. Buspirone, a partial 5-HT1A receptor agonist, produced parameter changes similar to those induced by anxiolytic benzodiazepines. 8-OH-DPAT, a full 5-HT1A receptor agonist, significantly increased transitions and locomotor activity but not % time. 5-HT3 receptor antagonists, ICS205-930 and MDL72222, did not have any effect on these parameters. 6. Methamphetamine (1-2 mg/kg, i.p.) increased all parameters, while caffeine increased only locomotor activity. 7. The present findings indicate that the modified light/dark transition test is very simple and easy to perform for testing the anxiolytic and anxiogenic effects of drugs.
Shimada
T
T
Department of Japanese Oriental (Kampo) Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Matsumoto
K
K
Osanai
M
M
Matsuda
H
H
Terasawa
K
K
Watanabe
H
H
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000139:chemically induced*; D002243:Carbolines / Q000494:pharmacology; D003624:Darkness; D008027:Light; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010852:Picrotoxin / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D014151:Anti-Anxiety Agents; D002243:Carbolines; D008694:Methamphetamine; D010852:Picrotoxin; D015016:Yohimbine; C024915:beta-carboline-3-carboxylic acid ethyl ester