Kest B, Mogil J S, Sternberg W F, Pechnick R N, Liebeskind J C
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles 90024, USA.
Pharmacol Biochem Behav. 1995 Apr;50(4):587-92. doi: 10.1016/0091-3057(94)00346-7.
The role of sigma receptors in antinociceptive processes remains equivocal, because previous sigma drugs also bind to PCP/NMDA and opiate receptors. The present study examined the antinociceptive effects of the high-affinity, sigma-selective ligand 1,3-di-o-tolylguanidine (DTG; 10, 15, and 20 mg/kg, IP) on tail-withdrawal latencies in mice. DTG produced significant but short-lived increases in withdrawal latencies at all dose levels. DTG also produced hypothermia, but this effect was dissociable from antinociception. The highly selective sigma ligand rimcazole (10 and 25 mg/kg, IP) antagonized DTG antinociception in a dose-dependent manner. The opiate antagonist naloxone and the PCP/NMDA antagonist MK-801 were, however, without effect. Haloperidol, which also binds to sigma receptors, increased withdrawal latencies but did not alter DTG antinociception. These data implicate sigma receptors as the site of DTG antinociception, and more generally support the distinction between sigma, opiate, and PCP/NMDA receptors.
σ受体在抗伤害感受过程中的作用仍不明确，因为先前的σ药物也能与苯环己哌啶/ N -甲基- D -天冬氨酸（PCP/NMDA）受体和阿片受体结合。本研究检测了高亲和力、σ选择性配体1,3 - 二邻甲苯基胍（DTG；10、15和20mg/kg，腹腔注射）对小鼠甩尾潜伏期的抗伤害感受作用。DTG在所有剂量水平下均使甩尾潜伏期显著增加，但持续时间较短。DTG还导致体温过低，但这种作用与抗伤害感受无关。高选择性σ配体利咪唑（10和25mg/kg，腹腔注射）以剂量依赖的方式拮抗DTG的抗伤害感受作用。然而，阿片拮抗剂纳洛酮和PCP/NMDA拮抗剂MK - 801却没有效果。同样与σ受体结合的氟哌啶醇增加了甩尾潜伏期，但并未改变DTG的抗伤害感受作用。这些数据表明σ受体是DTG抗伤害感受的作用位点，更广泛地支持了σ受体、阿片受体和PCP/NMDA受体之间的区别。
