Caffeine-induced expression of c-fos mRNA and NGFI-A mRNA in caudate putamen and in nucleus accumbens are differentially affected by the N-methyl-D-aspartate receptor antagonist MK-801.
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 enhancement 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 on IEGs depending on the region studied.
Svenningsson
P
P
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Johansson
B
B
Fredholm
B B
BB
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1; D016762:Genes, fos / Q000187:drug effects; D017874:Immediate-Early Proteins; D017403:In Situ Hybridization; D007700:Kinetics; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism*; D009928:Organ Specificity; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D011699:Putamen / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D014157:Transcription Factors / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D014157:Transcription Factors; D002110:Caffeine; D016291:Dizocilpine Maleate