LY 171555-induced hyperdefensiveness in the mouse does not implicate benzodiazepine receptors.
In naive mice the selective D2 agonist LY171555 dose-dependently (0.5-5 mg/kg) induces defensive responses toward non-aggressive conspecifics. In order to investigate possible anxiogenic properties of the D2 agonist, its behavioural effects were compared with those produced by the benzodiazepine receptor inverse agonist methyl-beta-carboline-3-carboxylate(beta-CCM) in the elevated plus maze and in social interactions with non-aggressive opponents. When tested in the elevated plus maze, mice injected with LY 171555 (0.005-1 mg/kg) showed no decrease either of the number of entries or of the time spent in the open arms. At 5 mg/kg an actual increase of these two measures was observed. By contrast, beta-CCM (1-3 mg/kg) dose-dependently decreased both the number of entries and the time spent in the open arms without altering locomotion. The effects of beta-CCM were antagonized by the benzodiazepine receptor antagonist RO 15-1788 (3 mg/kg) showing a selective involvement of benzodiazepine receptors in their modulation. On the other hand, beta-CCM, (1-3 mg/kg) did not produce significant effects on defensive behaviour of mice interacting with non-aggressive opponents and the defensive responses of mice treated with 1 mg/kg LY 171555 were not prevented by 5 mg/kg chlordiazepoxide. These results show that DA D2-mediated hyperdefensiveness and anxiety modulated by benzodiazepine receptors are unrelated phenomena and suggest that this behavioural response may represent a model of those forms of fear-related reaction that do not respond to benzodiazepine treatment.
Belzung
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Instituto di Psicobiologia e Psicofarmacologia (CNR), Roma, Italy.
Cabib
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Fabiani
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Tolentino
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Puglisi-Allegra
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S
D000374:Aggression / Q000187:drug effects*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology; D002707:Chlordiazepoxide / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D019257:Quinpirole; D011963:Receptors, GABA-A / Q000187:drug effects*; D012919:Social Behavior
D002243:Carbolines; D003292:Convulsants; D015259:Dopamine Agents; D004873:Ergolines; D011963:Receptors, GABA-A; D019257:Quinpirole; D005442:Flumazenil; D002707:Chlordiazepoxide; C036150:beta-carboline-3-carboxylic acid methyl ester