Copyright © 1998 by Institute of Pharmacology
Polish Academy of Sciences
Pol. J. Pharmacol., 1998, 50, 299-305
ISSN 1230-6002

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N6-2-(4-AMINOPHENYL)ETHYLADENOSINE (APNEA), A PUTATIVE ADENOSINE A3 RECEPTOR AGONIST, ENHANCES METHAMPHETAMINE-INDUCED DOPAMINE OUTFLOW IN RAT STRIATUM
Krystyna Gołembiowska#, Alicja Żylewska
Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland

N6-2-(4-aminophenyl)ethyladenosine (APNEA), a putative adenosine A3 receptor agonist, enhances methamphetamine-induced dopamine outflow in rat striatum. K. GOŁEMBIOWSKA, A. ŻYLEWSKA. Pol. J. Pharmacol., 1998, 50, 299-305.

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 µM it diminished MTH-induced DA overflow during first 2 h of the experiment (p < 0.05), but potently enhanced it at higher 100 µM 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 µM 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.

Key words: adenosine A3 receptor, DA and glutamate release, rat striatum, microdialysis, methamphetamine

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