Rady J J, Fujimoto J M
Research Service-151, VA Medical Center, Milwaukee, WI, USA.
Pharmacol Biochem Behav. 1996 Jun;54(2):363-9. doi: 10.1016/0091-3057(95)02150-7.
The tail-flick response is a spinal reflex that can be modulated by administration of antinociceptive agents supraspinally through activation of descending systems and involvement of the action of neurotransmitters in the spinal cord. Descending noradrenergic and serotonergic systems are involved in morphine (and other mu opioid receptor agonists)-induced antinociception. These descending systems, however, are not involved in supraspinal delta opioid receptor agonist-induced antinociception. Recently, a descending system mediated by spinal gamma-aminobutyric acid (GABA) A and B receptors has been demonstrated to be involved in the antinociceptive action of delta 1 opioid receptor agonists ([D-Pen2,5]enkephalin in ICR mice and [D-Pen2,5]enkephalin and heroin in Swiss-Webster mice). In the present study, the involvement of spinal GABAA receptors in the antinociceptive action of supraspinal delta 2 opioid receptor agonists, [D-Ser2]-Leu-enkephalin-Thr and 6-monoacetylmorphine, action was demonstrated. The intrathecal administration of GABAA receptor antagonists, bicuculline and picrotoxin, inhibited the antinociceptive action of both [D-Ser2]-Leu-enkephalin-Thr and 6-monoacetylmorphine given intracerebroventricularly. The intrathecal administration of 2-hydroxysaclofen, a GABAB receptor antagonist, had no effect. These studies suggest that supraspinal delta 2, like delta 1, opioid receptor action involves spinal GABAA receptors, but delta 2, unlike delta 1, action does not involve GABAB receptors. Thus, the supraspinal delta 1 agonist action (heroin, DPDPE) and the delta 2 agonist action (6MAM, DSLET) can be further differentiated by the selectivity of the spinal GABA receptors involved in Swiss-Webster mice.
甩尾反应是一种脊髓反射，可通过脊髓上给予抗伤害感受药物，激活下行系统并涉及神经递质在脊髓中的作用来调节。下行去甲肾上腺素能和5-羟色胺能系统参与吗啡（及其他μ阿片受体激动剂）诱导的抗伤害感受。然而，这些下行系统不参与脊髓上δ阿片受体激动剂诱导的抗伤害感受。最近，已证明由脊髓γ-氨基丁酸（GABA）A和B受体介导的下行系统参与δ1阿片受体激动剂（ICR小鼠中的[D- Pen2,5]脑啡肽以及瑞士韦伯斯特小鼠中的[D- Pen2,5]脑啡肽和海洛因）的抗伤害感受作用。在本研究中，证明了脊髓GABAA受体参与脊髓上δ2阿片受体激动剂[D-Ser2]-亮氨酸-脑啡肽-苏氨酸和6-单乙酰吗啡的抗伤害感受作用。鞘内给予GABAA受体拮抗剂荷包牡丹碱和印防己毒素，可抑制脑室内给予的[D-Ser2]-亮氨酸-脑啡肽-苏氨酸和6-单乙酰吗啡的抗伤害感受作用。鞘内给予GABAB受体拮抗剂2-羟基氯苯氨丁酸则无作用。这些研究表明，脊髓上δ2阿片受体的作用与δ1阿片受体一样，涉及脊髓GABAA受体，但δ2阿片受体的作用与δ1不同，不涉及GABAB受体。因此，在瑞士韦伯斯特小鼠中，脊髓上δ1激动剂作用（海洛因、DPDPE）和δ2激动剂作用（6MAM、DSLET）可通过所涉及的脊髓GABA受体的选择性进一步区分。
