DISPERSION CHARACTERISTICS OF [H-3] LABELED ADENOSINE AGONIST-ANTAGONIST FOLLOWING THEIR INTRASTRIATAL MICROINFUSION

Following their intrastriatal microinfusion, the dispersion patterns o f an adenosine receptor agonist (N-6-cyclohexyladenosine) and on antag onist (8-cyclopentyl-1,3-dipropylxanthine) within the striatal tissue were investigated in Sprague-Dawley rats. The [H-3]-labeled ligands we re microinfused into the striatum of conscious rats through preimplant ed guide cannulae in the volume of either 200 (0.1 mu Ci) or 1000 nl ( 0.5 mu Ci) and the animals were killed 15 or 30 min later. The diffusi on of the radioactive ligands was evaluated by measuring the radioacti vity 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 im mediate vicinity of microinfusion site regardless of the postmicroinfu sion time (15 or 30 min). The pattern of tissue diffusion was similar at 15 min after the intrastriatal microinfusion of 1000 nl of [H-3]-li gands. At 30 min after the intrastriatal microinfusion of 1000 nl volu me, a relatively larger area of striatal tissue was covered by the dru g solution. In addition, the 1000 nl intrastriatal microinfusion proba bly resulted in the diffusion of some of the drug solution into the ex trastriatal area since small but significant radioactivity was detecte d at sites outside the striatum. The intrastriatal diffusion of the [H -3]-ligand solution wa snot uniform in all directions from the site of microinfusion. The relationship between the amount of radioactivity r emaining at the site of microinfusion and the postmicroinfusion time w as inverse. Additionally, at the same postmicroinfusion time (15 or 30 min), a lower percent of the total microinfused radioactivity was fou nd remaining at the microinfusion site with the 1000 nl microinfusion volume than that with the 200 nl volume. Overall, the diffusion patter ns of intrastriatal adenosine agonist and antagonist were similar. The results of the present investigation suggest that both the microinfus ion volume and the postmicroinfusion time may be important factors in determining the diffusion pattern and tissue content of intrastriatall y microinfused adenosine drugs. This information could be important fo r the correct understanding and interpretation of the data from studie s involving drug microinfusions.