Combination of adenosine A1 and A2A receptor blocking agents induces caffeine-like locomotor stimulation in mice.
The spontaneous locomotor activity of C57BL/6J mice was examined, using an automated detection system based on infra-red beams, after administration of caffeine (3-30 mg/kg, i.p.), the adenosine A(2A) receptor selective antagonist SCH 58261 (0.312-2.5 mg/kg, i.p.) and the A(1) selective antagonist DPCPX (1.25-5 mg/kg, i.p.). SCH 58261 failed to influence motor activity in mice habituated to the test environment. DPCPX produced a small increase in motility and locomotion (significant at the dose of 5.0 mg/kg), much weaker than that produced by caffeine. Combined administration of DPCPX (1.2 mg/kg, i.p.) and SCH 58261 (1.2 mg/kg, i.p.) produced stimulation of motility and locomotion comparable with the effect of caffeine (15 mg/kg, i.p.). In contrast to motility and locomotion, rearing counts were not significantly influenced by DPCPX, SCH 58261, their combination, or by caffeine. Caffeine (15 mg/kg, i.p.) caused an increase in NGFI-A mRNA (an immediate early gene was chosen as an index of neuronal activation) in the piriform cortex 4 h after injection. This effect was reproduced by the combination of A(1) and A(2A) receptor antagonist. It is hypothesised that the stimulatory effect of low doses of caffeine in C57BL/6J mice is due to concomitant blockade of both A(1) and A(2A) adenosine receptors.
Kuzmin
Alexander
A
Department of Neuroscience, Karolinska Institutet, Sweden. alexander.kuzmin@neuro.ki.se
Johansson
Björn
B
Gimenez
Lydia
L
Ogren
Sven-Ove
SO
Fredholm
Bertil B
BB
D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis / Q000235:genetics; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D014230:Triazoles / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000697:Central Nervous System Stimulants; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D018696:Neuroprotective Agents; D011743:Pyrimidines; D012333:RNA, Messenger; D014230:Triazoles; D014970:Xanthines; D002110:Caffeine; C051360:1,3-dipropyl-8-cyclopentylxanthine