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Dopaminergic transmission and (+)amphetamine‐induced lethality in aggregated mice
Author(s) -
DuterteBoucher D.,
Duhamel F.,
Costentin J.
Publication year - 1992
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1992.tb00090.x
Subject(s) - lethality , amphetamine , dopaminergic , pharmacology , chemistry , neuroscience , medicine , biology , dopamine , toxicology
Summary— In aggregated mice the lethal dose 50% (LD50) of (+)amphetamine was found to be clearly lower than in isolated animals (dose ratio: 6:1), whereas with the pure dopamine uptake inhibitor GBR 12783, the ratio was only 2. Pretreatment of mice with GBR 12783 (20 or 40 mg/kg ip) did not reduce the lethality of (+)amphetamine (10 mg/kg) in aggregated mice. Taking into account their relative affinity for D1 and D2 dopamine receptors, various DA antagonists were opposed to (+)amphetamine (20 mg/kg) in aggregated mice. The specific D1 antagonist SCH 23390 was especially effective (ID 50 10μg/kg). The specific D2 antagonists (±) sulpiride and metoclopramide were effective for high doses (ID 50 = 43 and 19 mg/kg respectively). The dopamine antagonists haloperidol and α‐flupenthixol, less specific as regards D1 vs D2 receptors, had an ID 50 of 66 and 186 μg/kg respectively. Association of the D1 antagonist SCH 23390 with the D2 antagonist (±) sulpiride resulted in an apparent additive effect for reducing the (+)amphetamine‐induced lethality. A semi‐chronic treatment with either the D1 agonist SKF 38393 (7 times 20 mg/kg) or (+)amphetamine (6 times 10 mg/kg) performed in isolated mice did not reduce the lethality induced by (+)amphetamine (20 mg/kg) in aggregated mice. The antagonism of the (+)amphetamine‐induced lethality in aggregated mice, frequently used to screen meuroleptics, reveals their antagonistic activity towards D1 or D2 dopamine receptor types.