Abstract
Caffeine (100 mg/kg, i.p.) induces a rapid increase in the expression of mRNA for the immediate early genes (IEGs) c-fos and NGFI-A in rat striatum. We have examined how this response is affected by pretreatment with either the noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 (1 and 3 mg/kg, i.p.), the competitive NMDA receptor antagonist D-CPP (6 mg/kg, i.p.), or the non-selective excitatory amino acid receptor antagonist kynurenic acid (300 mg/kg, i.p.). The two NMDA receptor antagonists significantly reduced the caffeine-induced expression of both c-fos mRNA and NGFI-A mRNA in the medial part of the caudate putamen. The effect was less pronounced in the lateral part of the caudate putamen. MK-801 caused an enancement of c-fos and NGFI-A mRNA expression in nucleus accumbens. Pretreatment with kynurenic acid caused no marked alterations in the caffeine-induced expression of c-fos mRNA and NGFI-A mRNA in any brain region. These findings suggest that glutamatergic transmission via NMDA receptors contributes to the induction of c-fos mRNA and NGFI-A mRNA by caffeine in striatum. In addition we show that MK-801 can either increase or decrease the caffeine effect of IEGs depending on the region studied.
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