Caffeine mimics the effect of a dopamine D2/3 receptor agonist on the expression of immediate early genes in globus pallidus.
In order to evaluate the effect of caffeine on striatopallidal neurons we used in situ hybridization to examine the mRNA expression of the immediate early genes (IEGs), c-fos, fos B, c-jun, jun B, NGFI-A and NGFI-B in globus pallidus in rats given single or repeated administration of caffeine. A significant induction of c-fos mRNA, but not of any of the other IEGs, was found 2, 4 and 8 hr after a single injection of 50 mg/kg caffeine. Following repeated injections of caffeine for 2 weeks a single challenge with caffeine did not induce the expression of any of the studied genes. The ability of caffeine to increase pallidal c-fos mRNA expression was mimicked by the dopamine D2/3 receptor agonist quinpirole (1 or 3 mg/kg), whereas the dopamine D2/3 receptor antagonist raclopride (2 mg/kg) was ineffective. Caffeine and quinpirole did not have synergistic effects when given together. The caffeine-induced c-fos mRNA expression was not counteracted by concomitant treatment with raclopride. The present data provide evidence that acute treatment with caffeine reduces the activity of the striatopallidal neuron, and since this neuron is inhibitory the result is an increased activity in globus pallidus. The effect of blocking the striatal A2A receptors with caffeine is essentially identical to that observed after activation of dopamine D2 receptors, but is independent of these receptors. The fact that pallidal c-fos mRNA expression decreased upon repeated administration of caffeine may be related to the development of tolerance to locomotion stimulation that occurs following chronic caffeine ingestion.
Svenningsson
P
P
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. per.svenningsson@fyfa.ki.se
Fredholm
B B
BB
D000818:Animals; D001345:Autoradiography; D002110:Caffeine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D015870:Gene Expression / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D005917:Globus Pallidus / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D019257:Quinpirole / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D020891:Raclopride; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000235:genetics; D050637:Receptors, Dopamine D3; D012457:Salicylamides / Q000494:pharmacology
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493595:Drd3 protein, rat; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012457:Salicylamides; D019257:Quinpirole; D002110:Caffeine; D020891:Raclopride