安非他命(amphetamine, AMPH)是著名的厭食劑(anorectic agent)，而腦內的Y型神經胜肽(neuropeptide Y, NPY)則可增進食慾。AMPH的厭食作用，是否透過腦內NPY的調控？目前則仍未明。因此，本論文希望以此為探討的主題。
　　AMPH首次給藥時，可使大白鼠產生顯著的厭食作用，此時，下視丘NPY的含量也隨著減少；這項減少可由下視丘NPY的免疫染色(immunostaining)也看到。由此可知，腦內的NPY參與著AMPH的厭食作用。可是，AMPH若持續給藥時，則厭食作用會逐漸回復正常；本文稱此為「厭食耐受性(tolerant anorexia)」。這項厭食耐受性的產生也與腦內的NPY有關，因為：(1)厭食耐受性產生時，下視丘NPY的濃度會回復到正常。(2)NPY antisense注入側腦室時，可延緩厭食耐受性的形成。(3)腦內NPY過度表現時，可加速厭食耐受性的形成。
　　另一方面，AMPH會造成腦內NPY含量的改變，與腦內釋放的dopamine (DA) 去同時活化D1及D2 receptor有關。因為：(1) 使用D1或D2 blocker，均能阻斷AMPH的厭食作用。(2)使用a-methyl-p-tyrosine (tyrosine hydroxylase的 inhibitor)，可減少腦內DA的含量，並可加速AMPH厭食耐受性之形成。但是，使用nomifensine (DA reuptake 的inhibitor)，則可減緩之。(3) D1及D2 agonists合併給藥時，就能產生AMPH-like的作用。可是，D1或D2 agonist單獨給藥時，卻不能。(4)腦內NPY過度表現時，可減弱「D1及D2 agonists合併給藥」的厭食作用。
　　此外，AMPH厭食耐受性的形成，與血漿中insulin、leptin、glucocorticoid及glucose等似乎無關，因為：(1)血漿中insulin、 leptin及glucose濃度，在AMPH持續注射的動物並未改變。(2)腎上腺摘除的大白鼠，對AMPH厭食作用的反應，與假手術的大白鼠比較，並無差異；顯示glucocorticoid並未參與。
　　綜合以上結果，得知：腦內的NPY參與著AMPH的「厭食作用」及「厭食耐受性」之形成；這兩項作用與腦內釋放的DA去同時活化D1及D2 receptor有關。

　Amphetamine (AMPH) is known as an anorectic agent. Cerebral neuropeptide Y (NPY) is an appetite stimulant. The aim of the present study is to investigate whether cerebral NPY is involved in the anorectic action of AMPH.
　Rats given with AMPH produced an anorectic effect and a reduction of hypothalamic NPY contents. This reduction of NPY was also observed in the area of hypothalamic PVN by the immunocytochemical staining. These results revealed that cerebral NPY was involved in AMPH anorexia. However, rats given repeatedly with AMPH produced a reversion of food intake to normal (tolerant anorexia). Cerebral NPY was also involved in the induction of tolerant anorexia, due to (1) the reversion of hypothalamic NPY content was observed in rats with tolerant anorexia and (2) the induction of tolerant anorexia was inhibited by NPY antisense injected into brain and was promoted in transgenic mice with NPY over expression.
　Changes of NPY content by AMPH treatment were related to the cerebral released dopamine (DA) that co-activated D1 and D2 receptors. This was obtained from the facts that: (1) both D1 and D2 blockers inhibited AMPH-induced anorexia; (2) AMPH-induced tolerant anorexia was attenuated by a-methyl-p-tyrosine, the tyrosine hydroxylase inhibitor, but was increased by nomifensine, the DA reuptake inhibitor; (3) repeated treatment of D1/D2 agonists, but not D1 or D2 agonist alone, induced AMPH-like anorectic action; and (4) NPY over expression in mice reduced the D1/D2 agonist-induced anorexia.
　AMPH-induced tolerant anorexia was not related with the changes by plasma insulin, leptin, glucose and glucocorticoid. Plasma insulin, leptin or glucose remained no change during AMPH repeated treatment. The anorectic action of AMPH in adrenolectomized rats was the same as that of sham-operated control indicating there was no involvement of plasma glucocorticoid.
　In conclusion, it is suggested that cerebral NPY is involved in both the anorectic action and the tolerant anorexia induced by AMPH depending on the cerebral release of DA that can co-activate D1 and D2 receptors.

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