Determination of the effects of caffeine and carbamazepine on striatal dopamine release by in vivo microdialysis.
The effects of carbamazepine and caffeine on adenosine receptor subtypes were determined using in vivo microdialysis in an attempt to elucidate their different psychotropic mechanisms of action. Adenosine and a selective adenosine A1 receptor agonist decreased the striatal extracellular dopamine level, whereas caffeine, carbamazepine and a selective adenosine A1 receptor antagonist increased it, but neither an adenosine A2 receptor agonist nor an antagonist affected it. Under conditions of adenosine A1 receptor blockade, adenosine, carbamazepine and a selective adenosine A2 receptor agonist increased the striatal extracellular dopamine level, whereas caffeine and a selective adenosine A2 receptor antagonist decreased it. These results suggest that adenosine A1 receptor stimulation reduces the striatal extracellular dopamine level, and that adenosine A2 receptor stimulation under conditions of adenosine A1 receptor blockade increases it. Therefore, caffeine is an antagonist of both adenosine A1 and A2 receptor subtypes, and carbamazepine is an adenosine A1 receptor antagonist as well as an adenosine A2 receptor agonist. These properties support the hypothesis that the central actions of both carbamazepine and caffeine result from effects on both adenosine A1 and A2 receptors.
Okada
M
M
Department of Neuropsychiatry, Hirosaki University, Japan. okadamot@cc.hirosaki-u.ac.jp
Kiryu
K
K
Kawata
Y
Y
Mizuno
K
K
Wada
K
K
Tasaki
H
H
Kaneko
S
S
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008024:Ligands; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D000927:Anticonvulsants; D000697:Central Nervous System Stimulants; D008024:Ligands; D018047:Receptors, Purinergic P1; D002220:Carbamazepine; D002110:Caffeine; D000241:Adenosine; D004298:Dopamine