腺核?和催產素已經證實能降低大白鼠的攝食量。本論文即研究腺核?A1、A2a接受器在調節攝食行為中扮演之角色。首先將大白鼠食物剝奪24小時後由腦室注射0﹐1﹐5或10 ug的N6-cyclopentyladenosine (CPA, A1接受器致效劑 ) 及 CGS-21680 (CGS, A2a接受器致效劑) ，並測量120分鐘內的攝食量。結果指出注射10 ug CPA以及1﹐5﹐10 ug CGS 均能顯著地降低攝食 (p<0.01) 。雙重免疫化學染色結果顯示注射上述藥物2小時後，下視丘室旁核及視上核中催產素神經元表現cFos的百分比顯著高於控制組 (p<0.05-p<0.01)，表示活化A1、A2a接受器的確可增加催產素細胞活性。因此，為了探討CPA或CGS抑制攝食之機轉是否經由活化催產素神經元而達成，故在注射CPA或CGS之前先由腦室內給予催產素接受器拮抗劑d(CH2)5Tyr(Me)-Orn8-vasotocin，並偵測大白鼠攝食量的變化。結果發現CPA或CGS所誘導之攝食量降低並無法被阻斷。這些證據顯示腺核?透過中樞神經系統中A1、A2a接受器而達成厭食的效果。雖然活化中樞的腺核?A1、A2a接受器可增加催產素神經元活性，然而中樞的催產素可能不參與CPA或CGS所誘導之攝食量降低作用。; Adenosine and oxytocin have been reported to suppress food intake in rats. The purpose of the present study was to investigate the role of adenosine A1 and A2a receptors in the modulation of food intake. First, food intake during the first 120 min after intracerebroventricular (i.c.v) injection of N6-cyclopentyladenosine (CPA, A1 receptor agonist) or CGS-21680 (CGS, A2a receptor agonist) was measured in animals fasted for 24h. The results showed that i.c.v injection of CPA (10ug) or CGS (1, 5, and 10 ug) significantly reduced food intake (p<0.01). In a second experiment, rats were sacrificed by perfusion 120 min after drug injection and brain tissues were subjected to double-labeling immuncytochemistry of cFos and oxytocin. We found a significant increase in cFos expression in oxytocin neurons of the paraventricular and the supraoptic nuclei after CPA or CGS treatment (p<0.05-p<0.01), suggesting that these neurons were activated by adenosine receptor agonists. To further investigate whether CPA or CGS-induced anorexia was mediated by activation of oxytocin neurons, rats were pretreated with a selective oxytocin receptor antagonist d (CH2)5Tyr(Me)-Orn8-vasotocin. The results showed that pretreatment of oxytocin antagonist failed to blunt the effect of CPA or CGS on food intake. The results suggest that the anorectic effect of adenosine is mediated by A1 & A2a receptors in the central nervous system. Although activation of central adenosine A1 & A2a receptors was associated with increased activity of oxytocinergic neurons, central oxytocin unlikely plays a role in the suppression of food intake in CPA or CGS-treated animals.
