本研究室之前結果得知，腺核苷並非經由催產素神經元來達到抑制食 之行為。因此，本論文欲探討神經胜肽Y神經元在腺核苷接受器致效劑所誘導之厭食行為中所扮演得角色。先將大白鼠食物剝奪24小時，並在腦室注射藥物後立即讓大白鼠恢復進食，並記錄第1、2、3、4小時的攝食量。結果指出給予10μg /5ul神經胜肽Y無法阻斷10 μg/5ul N6-cyclopentyladenosine（CPA, A1 接受器致效劑）或 1 μg/5ul CGS21680（CGS, A2a接受器致效劑）所引起大白鼠之攝食量降低的作用（P>0.05）。在免疫化學染色結果顯示，食物剝奪24小時的大白鼠在腦室注射1、5、10μg CPA或CGS 2小時後，下視丘弓形核和室旁核神經胜肽Y的表現量並不受到影響（P>0.05），這些證據表示腺核?抑制攝之作用應與神經胜肽Y無關。接著利用雙重組織免疫化學在經腦室內注射秋水仙素的大白鼠腦中觀察神經胜肽Y細胞是否表現腺核苷接受器，結果發現神經胜肽Y與腺核苷接受器表現的位置非常接近，但無明確的證據顯示兩者共同存於同一神經元，因此更支持了前面之實驗結果，亦即腺核苷厭食之作用並不經由抑制神經胜肽Y神經元而達成。為更進一步探討內生性腺核苷對於攝食的調節作用，故在正常情形下由腦室給予1、5 及 10μg DPCPX（A1接受器拮抗劑）或ZM-2413851（ZM,A2a接受器拮抗劑），結果顯示注射10μg DPCPX能顯著增加攝食（P<0.05），但是ZM並不影響攝食量（P>0.05）。本研究顯示雖然內生性腺核苷A1接受器致效劑為一飽食因子，且在形態學上亦發現神胜肽Y神經元附近有腺核苷接受器；然而，神經胜肽Y神經元並不媒介外生性腺核苷所誘導的厭食作用。; Our previously study indicated that the inhibitory effect of adenosine on feeding is not mediated by oxytocin neurons. The purpose of the present study was to investigate the role of NPY neurons in adenosine receptor agonist-induced anorexia. We found that intracerebral co-administration of 10 μg/5ul N6-cyclopentyladenosine（CPA, A1 receptor agonist）or 1 μg/5ul CGS21680（CGS, A2a receptor agonist）with 10 μg/5ul NPY did not block the inhibitory effect of CPA or CGS-on food intake in overnight fasted rats（P>0.05）. Another set of animals were sacrificed 2h after icv injection of CPA or CGS（1, 5 and 10 μg）and brain tissues were subjected to immunocytochmistry of NPY . The results showed that adenosine failed to alter NPY levels in the hypothalamic Arcuate（ARC）and Paraventricular（PVN）nuclei. These data reveal that the anorectic effect of adenosine is not mediated by NPY neurons. In order to investigate whether NPY cell bodies express adenosine receptors, double-label immunocytochemistry was performed in brain tissues obtained from icv cholchicin-treated animals. The result showed that although NPY was in close apposition with adenosine receptor immunoreactivity, there was no evidence of colocalization of both antigens. To further investigate the role of endogenous adenosine in the modulation of food intake, satiated rats were treated icv with 1, 5 or 10 μg DPCPX（A1 receptor antagonist）or ZM-2413851（ZM, A2a receptor antagonist）. I found that 10ug DPCPX significantly increased food intake（P<0.05）, but ZM failed to alter the feeding behavior （P>0.05）. The data suggest that endogenous adenosine A1 receptor plays a role in normal feeding behavior and adenosine via A1 receptors may have the same target as NPY in PVN. However, exogenous adenosine-induced anorexia is not mediated by orexigenic NPY neurons.
