B-HT 920 antagonizes rat neophobia in the X-maze test: a comparative study with other drugs active on adrenergic and dopaminergic receptors.
Since there is compelling evidence to suggest a significant participation of central noradrenergic (NA) and dopaminergic (DA) pathways in the modulation of anxiety disorders, the possible tranquillizing effect of B-HT 920, considered to be a selective agonist of central DA autoreceptors at low doses, but also a stimulant of central alpha 2-receptors at high doses, was investigated by means of the X-maze test. For comparison, other drugs active on alpha-adrenoceptors and DA receptor subtypes were similarly tested. B-HT 920 at high doses (1 and 2 mg/kg) significantly antagonized the animals' spontaneous avoidance of open spaces (a sign indicative of anxiety), despite the reported sedative effects of the drug; it should be pointed out, however, that the latter were observable in our tests only at 1 mg/kg, a more pronounced sedation was the sole effect of a low dose (100 micrograms/kg) of B-HT 920. In our experimental conditions, clonidine (50 micrograms/kg) and yohimbine (5, but not 1 and 2.5 mg/kg) exerted anxiolytic and anxiogenic effects, respectively, in line with theoretical expectations and with results already published. DPI (100 and 200 micrograms/kg) (reported to be a selective agonist at DA receptors mediating neuronal inhibition and also active on alpha-adrenoceptors) and B-HT 958 (1 and 10 mg/kg) (a stimulant of DA autoreceptors but a blocker of alpha 2-adrenoceptors) were unable to modify the natural preference of rats for closed arms. Hypomotility was obtained with both doses of B-HT 958 and with the higher dose of DPI.
Ferrari
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F
Institute of Pharmacology, University of Modena, Italy.
Tartoni
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PL
Mangiafico
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D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D015259:Dopamine Agents; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D015016:Yohimbine; C024763:talipexole; D003000:Clonidine; D003891:Desipramine