Dispersion characteristics of [3H]-labeled adenosine agonist/antagonist following their intrastriatal microinfusion.
Following their intrastriatal microinfusion, the dispersion patterns of an adenosine receptor agonist (N6-cyclohexyladenosine) and an antagonist (8-cyclopentyl-1,3-dipropylxanthine) within the striatal tissue were investigated in Sprague-Dawley rats. The [3H]-labeled ligands were microinfused into the striatum of conscious rats through preimplanted guide cannulae in the volume of either 200 (0.1 microCi) or 1000 nl (0.5 microCi) and the animals were killed 15 or 30 min later. The diffusion of the radioactive ligands was evaluated by measuring the radioactivity in the striatal tissue samples using a tissue punching technique. When the volume of microinfusion was 200 nl, the diffusion within the striatum was limited as the radioactivity remained confined to the immediate vicinity of microinfusion site regardless of the postmicroinfusion time (15 or 30 min). The pattern of tissue diffusion was similar at 15 min after the intrastriatal microinfusion of 1000 nl of [3H]-ligands. At 30 min after the intrastriatal microinfusion of 1000 nl volume, a relatively larger area of striatal tissue was covered by the drug solution. In addition, the 1000 nl intrastriatal microinfusion probably resulted in the diffusion of some of the drug solution into the extrastriatal area since small but significant radioactivity was detected at sites outside the striatum. The intrastriatal diffusion of the [3H]-ligand solution was not uniform in all directions from the site of microinfusion. The relationship between the amount of radioactivity remaining at the site of microinfusion and the postmicroinfusion time was inverse. Additionally, at the same postmicroinfusion time (15 or 30 min), a lower percent of the total microinfused radioactivity was found remaining at the microinfusion site with the 1000 nl microinfusion volume than that with the 200 nl volume. Overall, the diffusion patterns of intrastriatal adenosine agonist and antagonist were similar. The results of the present investigation suggest that both the microinfusion volume and the postmicroinfusion time may be important factors in determining the diffusion pattern and tissue content of intrastriatally microinfused adenosine drugs. This information could be important for the correct understanding and interpretation of the data from studies involving drug microinfusions.
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC, USA.
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D000241:Adenosine / Q000819:agonists / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007553:Isotope Labeling; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium; D014970:Xanthines / Q000494:pharmacology*
D014970:Xanthines; D014316:Tritium; C027513:N(6)-cyclohexyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine