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.