N6-2-(4-aminophenyl)ethyladenosine (APNEA), a putative adenosine A3 receptor agonist, enhances methamphetamine-induced dopamine outflow in rat striatum.
In the present study, the effect of adenosine A3 receptor agonist, N6-2-(4-aminophenyl)ethyladenosine (APNEA), on methamphetamine (MTH)-induced dopamine (DA) release in rat striatum was evaluated using microdialysis in freely moving animals. MTH at a dose of 5 mg/kg injected 3-times every two hours produced massive overflow of DA and decline in the level of DOPAC (3,4-dihydroxyphenylacetic acid) and HVA (homovanillic acid). APNEA perfused locally to the striatum via microdialysis probe triggered opposite effects, at 75 microM it diminished MTH-induced DA overflow during first 2 h of the experiment (p<0.05), but potently enhanced it at higher 100 microM concentration for entire period of treatment (p<0.001). Concomitant release of glutamate in striatum was slightly decreased by MTH alone, and significantly diminished by coadministration of 100 M APNEA (p<0.001). The data indicate that activation of adenosine A3 receptor exerts rather toxic effect on DA neurons and exacerbates neurotoxicity of MTH. In addition, MTH-induced DA overflow does not seem to result from the increased release of striatal glutamate level.
Gołembiowska
K
K
Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Zylewska
A
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000633:toxicity; D004347:Drug Interactions; D004357:Drug Synergism; D018698:Glutamic Acid / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D017551:Microdialysis; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar; D043684:Receptor, Adenosine A3; D014793:Visual Cortex / Q000187:drug effects / Q000378:metabolism*
D002316:Cardiotonic Agents; D015259:Dopamine Agents; C086112:N(6)-2-(4-aminophenyl)ethyladenosine; D058906:Purinergic P1 Receptor Agonists; D043684:Receptor, Adenosine A3; D015102:3,4-Dihydroxyphenylacetic Acid; D018698:Glutamic Acid; D008694:Methamphetamine; D000241:Adenosine; D004298:Dopamine; D006719:Homovanillic Acid