Long-term caffeine treatment leads to a decreased susceptibility to NMDA-induced clonic seizures in mice without changes in adenosine A1 receptor number
1993; Elsevier BV; Volume: 612; Issue: 1-2 Linguagem: Inglês
10.1016/0006-8993(93)91672-f
ISSN1872-6240
AutoresVasil Georgiev, B. Johansson, Bertil B. Fredholm,
Tópico(s)Neurological disorders and treatments
ResumoThe effects of long-term caffeine treatment onN-methyl-d-aspartate (NMDA)-induced seizures in mice were studied. Caffeine was added (0.3 g/1) to drinking water for 14 days and the mice ingested 60–70 mg/kg/day. During the treatment, the plasma concentrations of methylxanthines (caffeine, theophylline and/or paraxanthine, theobromine) were measured. NMDA (150 mg/kg i.p.) was administered to control mice and to mice during and after the caffeine administration. A1 adenosine receptor density in the gyrus dentatus of hippocampus, measured by quantitative receptor autoradiography with [3H]cyclohexyl adenosine as the ligand, was not significantly altered after long-term caffeine treatment. NMDA-induced clonic seizures, wet dog shakes and mortality were significantly reduced at the end of long-term caffeine treatment but returned towards control at 1 and 2 days after withdrawal. At the end of caffeine treatment, tonic seizures were also absent. These results show that long-term treatment with caffeine in a dose that gives plasma levels of 6–10 μM decreases the effects of NMDA on e.g. seizure susceptibility, and that this effect cannot be ascribed to changes of A1 adenosine receptor density.
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