A two-compartment exploratory model to study anxiolytic/anxiogenic effects of drugs in the rat.
The response of a recently described light/dark choice novelty situation to anxiolytic and non-anxiolytic agents as well as to putative anxiogenic drugs was assessed in rats. Diazepam (1.0-10.0 mg/kg, i.p.), chlordiazepoxide (2.5-10.0 mg/kg, i.p.), and pentobarbital (pentobarbitone) (7.5-15.0 mg/kg, i.p.) enhanced rats' activity in the dark and brightly lit compartments as well as crossings between the two, while imipramine (5-20 mg/kg, i.p.) had no effects. None of these drugs changed animal locomotion in activity cages. d-Amphetamine (1.5 mg/kg, i.p.) caused a significant increase in the three parameters used to measure rats' exploratory activity, but the effect was due to an increase in the general activity of the animal. No tolerance to the effects of diazepam developed after daily treatment with 5 mg/kg i.p. for 15 days. Non-sedative and non-convulsant doses of putative anxiogenic drugs such as yohimbine (2.5-5.0 mg/kg, i.p.), picrotoxin (2.0-4.0 mg/ml, i.p.) and ethyl-beta-carboline-3-carboxylate (2.5-5 mg/kg, i.p.) reduced the exploratory activity of rats in the dark compartment. The advantages and problems of using this test to identify anxiolytic and anxiogenic drugs are discussed.
Merlo Pich
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E
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Samanin
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R
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000139:chemically induced* / Q000523:psychology; D002243:Carbolines / Q000494:pharmacology; D002707:Chlordiazepoxide / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects*; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D008960:Models, Psychological; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015016:Yohimbine / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D002243:Carbolines; D002707:Chlordiazepoxide; D003913:Dextroamphetamine; D003975:Diazepam; D007099:Imipramine; D010424:Pentobarbital; D010852:Picrotoxin; D015016:Yohimbine; C024915:beta-carboline-3-carboxylic acid ethyl ester