Behavioural and neurochemical evidence that the antimicrobial agent oxolinic acid is a dopamine uptake inhibitor
| Autor: | J.-M. Vaugeois, J. Garcia de Mateos-Verchere, Jean Costentin, B. Naudin |
|---|---|
| Přispěvatelé: | Unité de neuropsychopharmacologie expérimentale (ESA 6036), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 1999 |
| Předmět: |
Male
Dextroamphetamine Reserpine Mice Inbred Strains Pharmacology Motor Activity 03 medical and health sciences chemistry.chemical_compound Mice Radioligand Assay 0302 clinical medicine Anti-Infective Agents Dopamine Uptake Inhibitors Dopamine Uptake Complex Dopamine Oxolinic acid Haloperidol medicine Animals Pharmacology (medical) Biological Psychiatry 030304 developmental biology 0303 health sciences SCH-23390 Dose-Response Relationship Drug Oxolinic Acid Benzazepines Corpus Striatum 3. Good health Rats Psychiatry and Mental health Neurology chemistry Dopamine Antagonists Neurology (clinical) 030217 neurology & neurosurgery [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology medicine.drug |
| Zdroj: | European Neuropsychopharmacology the Journal of the European College of Neuropsychopharmacology European Neuropsychopharmacology the Journal of the European College of Neuropsychopharmacology, 1998, 8 (4), pp.255-9. ⟨10.1016/s0924-977x(97)00083-7⟩ |
| ISSN: | 0924-977X |
| DOI: | 10.1016/s0924-977x(97)00083-7⟩ |
| Popis: | The antimicrobial agent oxolinic acid, injected i.p. in mice, induced a dose dependent increase in locomotor activity. This stimulation culminated at the 32 mg/kg dose and became smaller for higher doses (64-128 mg/kg). When opposed to increasing doses (50-100-200 microg/kg i.p.) of haloperidol (D2 dopamine receptor antagonist), the stimulant locomotor effect of 32 mg/kg oxolinic acid was not significantly reversed. On the contrary increasing doses (7.5-15-30 microg/kg s.c.) of SCH 23390 (D1 dopamine receptor antagonist) inhibited the stimulant locomotor effect. In mice made completely akinetic by a pretreatment with reserpine (4 mg/kg s.c., 18 h before testing), dexamphetamine (2 mg/kg s.c.) reversed this akinesia and even displayed a stimulant activity, similar to that observed in mice not treated by reserpine. On the contrary, oxolinic acid (32 mg/kg) did not reverse the reserpine induced akinesia and even opposed the reversion induced by dexamphetamine. In a synaptosomal fraction prepared from striatum of rats, oxolinic acid inhibited the 3H dopamine uptake with an IC50 = 4.3+/-0.6 x 10(-6) M. Finally, in mice injected i.v. with a tracer dose of 3H WIN 35428 (1 microCi) (a dopamine uptake blocker), 32 mg/kg oxolinic acid, i.p. administered, reduced by about 50% the specific binding of the radioligand to striatal dopamine carriers. It is concluded that the stimulant locomotor effect of oxolinic acid depends on the blockade of the neuronal dopamine uptake complex. |
| Databáze: | OpenAIRE |
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