Holmes B B, Fujimoto J M
Research Service, VA Medical Center, Milwaukee, WI.
Pharmacol Biochem Behav. 1994 Nov;49(3):675-82. doi: 10.1016/0091-3057(94)90087-6.
Intracerebroventricular (ICV) administration of [D-Pen2-D-Pen5]enkephalin (DPDPE), a delta opioid receptor agonist, activates a descending antinociceptive pathway that inhibits the tail-flick response in mice. Involvement of spinal GABA receptors in this response was studied by giving GABA antagonist intrathecally. First, antinociception produced by intrathecally administered isoguvacine, a GABAA agonist, was inhibited by intrathecal bicuculline (GABA receptor antagonist) or picrotoxin (chloride channel antagonist). Then, antinociception induced by ICV DPDPE was antagonized by intrathecal picrotoxin and bicuculline in a dose-and time-dependent manner. Second, intrathecal administration of 2-hydroxysaclofen, a GABAB antagonist (which inhibited antinociception induced by a GABAB agonist, baclofen, given IT), produced a shift of the dose-response curve for ICV DPDPE to the right. GABAA agonist, baclofen, given IT), produced a shift of the dose-response curve for ICV DPDPE to the right. GABAA and B antagonists given together intrathecally produced a greater than additive antagonistic effect against ICV DPDPE-induced antinociception. Thus, the delta agonist action of DPDPE in the brain leads to activation of descending spinal pathways which involve mediation by spinal GABAA and GABAB receptors in the antinociceptive response.
脑室内（ICV）注射δ阿片受体激动剂[D-青霉胺2-D-青霉胺5]脑啡肽（DPDPE）可激活一条下行性抗伤害感受通路，该通路能抑制小鼠的甩尾反应。通过鞘内注射GABA拮抗剂来研究脊髓GABA受体在这一反应中的作用。首先，鞘内注射GABAA激动剂异鹅肌肽所产生的抗伤害感受作用，被鞘内注射荷包牡丹碱（GABA受体拮抗剂）或印防己毒素（氯离子通道拮抗剂）所抑制。然后，鞘内注射印防己毒素和荷包牡丹碱以剂量和时间依赖性方式拮抗ICV DPDPE诱导的抗伤害感受作用。其次，鞘内注射GABAB拮抗剂2-羟基舒氯芬（其抑制鞘内注射GABAB激动剂巴氯芬所诱导的抗伤害感受作用）使ICV DPDPE的剂量-反应曲线右移。鞘内注射GABAA激动剂巴氯芬使ICV DPDPE的剂量-反应曲线右移。鞘内同时给予GABAA和B拮抗剂对ICV DPDPE诱导的抗伤害感受作用产生大于相加的拮抗效应。因此，DPDPE在脑中的δ激动剂作用导致下行脊髓通路的激活，该通路在抗伤害感受反应中涉及脊髓GABAA和GABAB受体的介导。
