Walker M J, Poulos C X, Le A D
Addiction Research Foundation, Toronto, Ontario, Canada.
Psychopharmacology (Berl). 1994 Jan;113(3-4):527-33. doi: 10.1007/BF02245234.
Several studies have demonstrated a paradoxical form of antinociception induced by the repeated administration of opioid antagonists accompanied by exposure to a painful stimulus. The underlying mechanism of this naloxone-induced antinociception (NIA) is still unknown, but the results of several studies suggest that it is a non-opioid response. This study was designed to investigate serotonergic and noradrenergic involvement in NIA. Rats were treated daily with systemic injections of 5 mg/kg naloxone, followed by a 45-s hot plate test of nociception (temperature = 51.5 +/- 0.5 degree C). After rats reached plateau levels of NIA, they received a test trial in which they were treated with various doses of different selective 5-HT or alpha 2 adrenoceptor antagonists in addition to naloxone before the hot plate test. Rats treated with 0.16, 0.32 and 0.63 mg/kg pirenperone or 2.5 mg/kg ritanserin showed significant reductions in paw lick latency with respect to rats treated with vehicle. In addition, high doses of yohimbine (7.5-10 mg/kg) also effectively reversed NIA. In contrast, NIA was not affected by acute blockade of 5-HT1 or 5-HT3 receptors by methiothepin or MDL 72222, respectively, or by the alpha 2 adrenoceptor blocker idazoxan. None of the 5-HT or alpha 2 adrenoceptor antagonists had any effect on the paw lick latencies of saline-treated rats. A possible role of 5-HT2 receptors in the antinociception induced by opioid receptor blockade is discussed.
多项研究表明，反复给予阿片类拮抗剂并同时暴露于疼痛刺激下会诱发一种矛盾形式的抗伤害感受。这种纳洛酮诱发的抗伤害感受（NIA）的潜在机制尚不清楚，但多项研究结果表明这是一种非阿片类反应。本研究旨在调查5-羟色胺能和去甲肾上腺素能在NIA中的作用。每天给大鼠全身注射5mg/kg纳洛酮，随后进行45秒的热板伤害感受测试（温度=51.5±0.5摄氏度）。在大鼠达到NIA的稳定水平后，进行一次测试试验，即在热板测试前，除了给予纳洛酮外，还给予它们不同剂量的不同选择性5-羟色胺或α2肾上腺素能受体拮抗剂进行治疗。用0.16、0.32和0.63mg/kg的匹泮哌隆或2.5mg/kg的利坦色林治疗的大鼠，与用赋形剂治疗的大鼠相比，爪舔潜伏期显著缩短。此外，高剂量的育亨宾（7.5-10mg/kg）也能有效逆转NIA。相比之下，分别用甲硫哒嗪或MDL 72222对5-HT1或5-HT3受体进行急性阻断，或用α2肾上腺素能受体阻滞剂咪唑克生，均不影响NIA。5-羟色胺或α2肾上腺素能受体拮抗剂对用生理盐水治疗的大鼠的爪舔潜伏期均无任何影响。本文讨论了5-HT2受体在阿片受体阻断诱发的抗伤害感受中的可能作用。
