Marek Gerard J
Department of Psychiatry, Yale School of Medicine, New Haven, CT 06508, USA.
Eur J Pharmacol. 2003 Aug 1;474(1):77-83. doi: 10.1016/s0014-2999(03)01971-x.
Electrophysiological studies have demonstrated a physiological interaction between 5-HT2A and mu-opioid receptors in the medial prefrontal cortex. Furthermore, behavioral studies have found that phenethylamine hallucinogens induce head shakes when directly administered into the medial prefrontal cortex. The receptor(s) by which morphine suppresses head shakes induced by serotonin agonists have not been characterized. We administered mu-opioid receptor agonists and antagonists to adult male Sprague-Dawley rats prior to treatment with the phenethylamine hallucinogen 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), which is known to induce head shakes via 5-HT2A receptors. The suppressant action of the moderately selective mu-opioid receptor agonist, buprenorphine (ID50 approximately 0.005 mg/kg, i.p.; a mu-opioid receptor partial agonist and kappa-opioid receptor antagonist) was blocked by naloxone and pretreatment with the irreversible mu-opioid receptor antagonist clocinnamox. Another mu-opioid receptor agonist fentanyl also suppressed DOI-induced head shakes. In contrast, a delta-opioid receptor agonist was without effect on DOI-induced head shakes. Thus, activation of mu-opioid receptors can suppress head shakes induced by hallucinogenic drugs.
电生理研究已证实在内侧前额叶皮质中5-HT2A与μ-阿片受体之间存在生理相互作用。此外，行为学研究发现，苯乙胺类致幻剂直接注入内侧前额叶皮质时会诱发头部震颤。吗啡抑制5-羟色胺激动剂诱发的头部震颤所涉及的受体尚未明确。在用苯乙胺类致幻剂1-(2,5-二甲氧基-4-碘苯基)-2-氨基丙烷（DOI）处理成年雄性Sprague-Dawley大鼠之前，我们先给它们施用了μ-阿片受体激动剂和拮抗剂，已知DOI通过5-HT2A受体诱发头部震颤。中度选择性μ-阿片受体激动剂丁丙诺啡（腹腔注射半数抑制剂量约为0.005mg/kg；一种μ-阿片受体部分激动剂和κ-阿片受体拮抗剂）的抑制作用被纳洛酮和不可逆μ-阿片受体拮抗剂氯辛肟预处理所阻断。另一种μ-阿片受体激动剂芬太尼也能抑制DOI诱发的头部震颤。相比之下，δ-阿片受体激动剂对DOI诱发的头部震颤没有影响。因此，μ-阿片受体的激活可以抑制致幻药物诱发的头部震颤。
