Behavioral analysis of zopiclone on the basis of their discriminative stimulus properties in the rat.
Zopiclone is a new cyclopyrrolone derivative which exerts pharmacological activities similar to those of benzodiazepines in behavioral and biochemical studies. In order to clarify the discriminative stimulus properties of zopiclone, 8 rats were trained to discriminate the interoceptive stimulus induced by zopiclone (3.2 mg/kg, i.p.) from those of saline. Following discrimination acquisition, administration of zopiclone resulted in drug-appropriate responding with an ED50 of 1.3 (1.0-1.8) mg/kg. The zopiclone discriminative stimulus generalized to the benzodiazepines diazepam (1.8 mg/kg), nitrazepam (10 mg/kg) and alprazolam (10 mg/kg). A non-benzodiazepine, suriclone, at 3.2 mg/kg, generalized to the zopiclone stimulus in 5 out of 7 rats, but meprobamate, hydroxyzine, tracazolate and muscimol did not. The benzodiazepine antagonist Ro 15-1788 (1 mg/kg) completely blocked zopiclone stimulus. In contrast, however, bicuculline and pentetrazol failed to antagonize it. The serotonin antagonist cinanserin and ritanserin neither generalized to the zopiclone stimulus nor did they exhibit antagonism. These results suggest that the zopiclone discriminative stimulus is mediated by binding to benzodiazepine receptors and appears not to be related to GABAergic or serotonergic system.
Yamamoto
T
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Kumasaka
Y
Y
Ueki
S
S
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D053961:Azabicyclo Compounds; D001522:Behavior, Animal / Q000187:drug effects*; D001569:Benzodiazepines / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009287:Naphthyridines; D010433:Pentylenetetrazole / Q000494:pharmacology; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D016713:Ritanserin; D012702:Serotonin Antagonists / Q000494:pharmacology; D013457:Sulfur Compounds
D014151:Anti-Anxiety Agents; D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D009287:Naphthyridines; D010879:Piperazines; D010880:Piperidines; D012702:Serotonin Antagonists; D013457:Sulfur Compounds; C515050:zopiclone; D001569:Benzodiazepines; D016713:Ritanserin; D009118:Muscimol; D005442:Flumazenil; C037283:suriclone; D010433:Pentylenetetrazole; D001640:Bicuculline