嗎啡是由鴉片提煉的一種生物鹼，經由腦內的作用而產生鎮靜與止痛效果。文獻指出嗎啡與血清素皆會造成血糖上升。然而，血清素是否參與嗎啡所造成的升糖作用，目前仍未清楚。因此，本研究目的欲探討血清素在嗎啡所誘導產生高血糖時所扮演的角色。結果顯示以靜脈注射大白鼠嗎啡或血清素之後，血糖皆有顯著增加的現象，此現象在腎上腺摘除或脊髓截斷後會被抑制。接著，先以腹腔注射5HT2A抑制劑ketanserin可阻斷嗎啡所引發血糖上升作用，但若先給予5HT2C的抑制劑RS102221，則無法產生抑制效果。相反地，以側腦室注射先投予RS102221可減弱嗎啡所造成血糖上升作用，然而，若先投予ketanserin，則嗎啡血糖上升作用不被減弱。上述結果可知嗎啡所引起的高血糖可能與血清素受體調節有關。文獻亦指出嗎啡是透過嗎啡μ型接受體升高血糖。在本實驗中，則以腹腔或側腦室注射嗎啡μ型接受體拮抗劑naloxonazine，結果發現升高的血糖有減弱的現象。接著，將嗎啡更換成血清素，亦發現升血糖作用有被減弱現象。嗎啡μ型受體剔除小鼠以靜脈方式投予嗎啡，亦發現血糖升高作用也有被減弱。已知嗎啡或血清素所造成高血糖的作用，皆經由釋放腎上腺素導致。於是，先以腹腔注射β阻斷劑propranolol，再投予嗎啡或血清素，發現確實能減弱嗎啡或血清素造成的高血糖作用。最後，先以腹腔注射大白鼠血清素合成的阻斷物p-chlorophenylalanine (PCPA)，結果發現會減弱嗎啡所產生的高血糖現象；此顯示嗎啡的血糖升高作用會因體內血清素合成受到抑制而減弱。綜合實驗的結果指出嗎啡造成的血糖上升現象主要是經由內生性血清素所致的機轉。

Morphine is one of the alkaloids extracted from opium, which induces sedative and narcotic effects through central nervous system. Previous studies indicate that both morphine and serotonin (5-HT) have the hyperglycemic effects. However, it is still unclear whether 5-HT affects hyperglycemia evoked by morphine. This study aimed to investigate the role of 5-HT in morphine-induced hyperglycemia.The results show that morphine and 5-HT produced a significant rise on blood glucose level but were decreased in those adrenalectomized or spinal cord truncation rats. The, morphine-induced hyperglycemic effect on rats can be blocked by i.p. ketanserin (a 5HT2A antagonist), instead of RS102221 (5HT2C antagonist). The hyperglycemia induced by i.c.v. morphine can be attenuated by RS102221, whereas ketanserin does not affect in morphine-induced hyperglycemia. These results suggest that the morphine-induced hyperglycemia is related to 5-HT action via serotonin receptor activation. Some studies indicate that morphine-induces hyperglycemia through opioid-μ receptor. In this study, the hyperglycemia in response to i.c.v. morphine was reduced by naloxonazine (μ-opioid receptor antagonist). The reduced plasma glucose level was observed in μ-opioid receptor knockout mice (KO mice) treated by i.v. naloxonazine. It is well known that the hyperglycemia to morphine or 5-HT by epinephrine release. We also found that propranolol, a β receptor blocker, reduced the hyperglycemia induced by both morphine and 5-HT. The morphine-induced hyperglycemia can be attenuated by i.p. administration of p-chlorophenylalanine (PCPA, an inhibitor of 5-HT biosynthesis), suggested that the morphine-induced hyperglycemia was mediated by 5-HT biosynthesis. In conclusion the endogenous 5-HT release play a pivotal role in morphine-induced hyperglycemia.

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