Killian P, Holmes B B, Takemori A E, Portoghese P S, Fujimoto J M
Research Service, Veteran's Affairs Medical Center, Milwaukee, Wisconsin, USA.
J Pharmacol Exp Ther. 1995 Aug;274(2):730-4.
Cold water swim stress for 3 min at 5 degrees C produces antinociception in the tail-flick test in mice by activation of delta opioid receptors in the brain. Also, the inhibition of the tail-flick reflex produced by i.c.v. administration of delta opioid receptor agonists is known to be mediated by spinal gamma-aminobutyric acid (GABA) receptors. The purpose of this investigation was to determine if the cold water swim stress-induced antinociceptive response is mediated by GABA receptors in the spinal cord. First, i.c.v. administration of the delta-2 receptor antagonist, naltriben, but not the delta-1 receptor antagonist, 7-benzylidenenaltrexone, antagonized the cold water swim stress-induced antinociception in ICR mice and confirmed the role of delta-2 receptors in this response. Next, the involvement of spinal GABAA receptors was shown through intrathecal administration of GABAA receptor antagonists, picrotoxin and bicuculline, which inhibited the cold water swim stress-induced antinociceptive response. Thus, the antinociception produced through activation of the delta-2 receptor in the brain by cold water swim stress involved a descending pathway mediated by spinal GABAA receptors. This descending pathway appeared to be the same as that activated by i.c.v. administration of delta-2 opioid agonists in the brain.
在5摄氏度的冷水中游泳应激3分钟，通过激活小鼠大脑中的δ阿片受体，在甩尾试验中产生抗伤害感受作用。此外，已知脑室内给予δ阿片受体激动剂所产生的甩尾反射抑制是由脊髓γ-氨基丁酸（GABA）受体介导的。本研究的目的是确定冷水游泳应激诱导的抗伤害感受反应是否由脊髓中的GABA受体介导。首先，脑室内给予δ2受体拮抗剂纳曲苄，但不是δ1受体拮抗剂7-苄叉基纳曲酮，可拮抗ICR小鼠冷水游泳应激诱导的抗伤害感受作用，并证实了δ2受体在该反应中的作用。其次，通过鞘内给予GABAA受体拮抗剂印防己毒素和荷包牡丹碱显示脊髓GABAA受体的参与，它们抑制了冷水游泳应激诱导的抗伤害感受反应。因此，冷水游泳应激通过激活大脑中的δ2受体产生的抗伤害感受作用涉及由脊髓GABAA受体介导的下行通路。该下行通路似乎与脑室内给予δ2阿片激动剂所激活的通路相同。
