Palotai Miklós, Adamik Agnes, Telegdy Gyula
Department of Pathophysiology, Faculty of Medicine, University of Szeged, Semmelweis Str. 1, Szeged, 6701, Hungary.
Neurochem Res. 2014 Aug;39(8):1477-83. doi: 10.1007/s11064-014-1337-8. Epub 2014 Jun 4.
The nociceptin/orphanin FQ peptide (NOP) receptor and its endogenous ligand plays role in several physiologic functions of the central nervous system, including pain, locomotion, anxiety and depression, reward and drug addiction, learning and memory. Previous studies demonstrated that the NOP-receptor system induces impairment in memory and learning. However, we have little evidence about the underlying neuromodulation. The aim of the present study was to investigate the involvement of distinct neurotransmitters in the action of the selective NOP receptor agonist orphan G protein-coupled receptor (GPCR) SP9155 P550 on memory consolidation in a passive avoidance learning test in rats. Accordingly, rats were pretreated with a nonselective muscarinic acetylcholine receptor antagonist, atropine, a γ-aminobutyric acid subunit A (GABA-A) receptor antagonist, bicuculline, a D2, D3, D4 dopamine receptor antagonist, haloperidol, a nonselective opioid receptor antagonist, naloxone, a non-specific nitric oxide synthase inhibitor, nitro-L-arginine, a nonselective α-adrenergic receptor antagonist, phenoxybenzamine and a β-adrenergic receptor antagonist, propranolol. Atropine, bicuculline, naloxone and phenoxybenzamine reversed the orphan GPCR SP9155 P550-induced memory impairment, whereas propranolol, haloperidol and nitro-L-arginine were ineffective. Our results suggest that the NOP system-induced impairment of memory consolidation is mediated through muscarinic cholinergic, GABA-A-ergic, opioid and α-adrenergic receptors, whereas β-adrenergic, D2, D3, D4-dopaminergic and nitrergic mechanisms are not be implicated.
痛敏肽/孤啡肽FQ肽（NOP）受体及其内源性配体在中枢神经系统的多种生理功能中发挥作用，包括疼痛、运动、焦虑和抑郁、奖赏与药物成瘾、学习和记忆。先前的研究表明，NOP受体系统会导致记忆和学习障碍。然而，我们对其潜在的神经调节作用了解甚少。本研究的目的是在大鼠被动回避学习试验中，研究不同神经递质在选择性NOP受体激动剂孤儿G蛋白偶联受体（GPCR）SP9155 P550对记忆巩固作用中的参与情况。因此，给大鼠预先使用了非选择性毒蕈碱型乙酰胆碱受体拮抗剂阿托品、γ-氨基丁酸A亚基（GABA-A）受体拮抗剂荷包牡丹碱、D2、D3、D4多巴胺受体拮抗剂氟哌啶醇、非选择性阿片受体拮抗剂纳洛酮、非特异性一氧化氮合酶抑制剂硝基-L-精氨酸、非选择性α-肾上腺素能受体拮抗剂酚苄明和β-肾上腺素能受体拮抗剂普萘洛尔。阿托品、荷包牡丹碱、纳洛酮和酚苄明可逆转孤儿GPCR SP9155 P550诱导的记忆障碍，而普萘洛尔、氟哌啶醇和硝基-L-精氨酸则无效。我们的结果表明，NOP系统诱导的记忆巩固障碍是通过毒蕈碱胆碱能、GABA-A能、阿片和α-肾上腺素能受体介导的，而β-肾上腺素能、D2、D3、D4多巴胺能和一氧化氮能机制未参与其中。
