Biphasic changes in locomotor behavior and in expression of mRNA for NGFI-A and NGFI-B in rat striatum following acute caffeine administration.
The time course of expression of mRNA for NGFI-A and NGFI-B after a single intraperitoneal injection of saline or caffeine was examined using in situ hybridization. Administration of a high dose of caffeine (100 mg/kg) decreased locomotor behavior and increased NGFI-A and NGFI-B mRNA in the entire striatum. A lower dose of caffeine (50 mg/kg) caused a weak enhancement of both messages, which was confined to the lateral part of caudate-putamen. This dose increased horizontal, but not vertical, movement. In rats treated with the lowest dose of caffeine (25 mg/kg), the expression of both investigated genes tended to be lower than for saline-treated rats and both horizontal and vertical locomotor activity increased markedly. The reduction in the number of labeled neurons seemed to occur predominantly in enkephalin-containing neurons, which coexpress adenosine A2A receptors and dopamine D2 receptors. The decrease of mRNA for NGFI-A, NGFI-B, and jun B caused by caffeine (25 mg/kg) could be mimicked by the D2 agonist quinpirole (1 and 3 mg/kg). Moreover, caffeine could significantly decrease the expression seen following treatment with the D2 antagonist raclopride (2 mg/kg). In addition, in the parietal cortex, 25 mg/kg of caffeine caused a significant elevation of both examined immediate early genes. Thus, biphasic changes in locomotion induced by caffeine are paralleled by biphasic changes in mRNA for NGFI-A, NGFI-B, and jun B. The results also provide additional support for a functionally important interaction between adenosine and dopamine D2 receptors.
D000818:Animals; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004338:Drug Combinations; D051766:Early Growth Response Protein 1; D004873:Ergolines / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D017874:Immediate-Early Proteins; D017403:In Situ Hybridization; D007267:Injections; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D019257:Quinpirole; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D012457:Salicylamides / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D004338:Drug Combinations; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D004873:Ergolines; D017874:Immediate-Early Proteins; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D012457:Salicylamides; D014157:Transcription Factors; D019257:Quinpirole; D002110:Caffeine; D020891:Raclopride