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Dopamine D1 and D2 receptors mediate analgesic and hypnotic effects of l-tetrahydropalmatine in a mouse neuropathic pain model.
Psychopharmacology (Berl). 2019 Nov; 236(11):3169-3182.P

Abstract

RATIONALE

Levo-tetrahydropalmatine (l-THP), an active ingredient of Corydalis yanhusuo, has been reported to be a partial agonist for dopamine D1 receptors (D1R) and an antagonist for D2R. Although it has been safely used clinically in China for decades as an analgesic with sedative/hypnotic properties, there are few studies that address the mechanisms by which l-THP exerts its beneficial effects in chronic pain-induced sleep disturbance.

OBJECTIVES

To investigate the effects and mechanisms of l-THP on sleep disturbance in a neuropathic pain-like condition.

METHODS

A mouse model of chronic neuropathic pain induced by partial sciatic nerve ligation (PSNL) was employed. The antinociceptive and hypnotic effects of l-THP were evaluated by measurement of mechanical allodynia, thermal hyperalgesia, and electroencephalogram (EEG) recordings in PSNL mice. Pharmacological approaches and c-Fos expression were used to clarify the mechanisms of l-THP.

RESULTS

Intraperitoneal injection of l-THP at 5 and 10 mg/kg not only significantly increased the mechanical threshold by 134.4% and 174.8%, and prolonged the thermal latency by 49.4% and 69.2%, but also increased non-rapid eye movement sleep by 17.5% and 29.6%, and decreased sleep fragmentation in PSNL mice, compared with the vehicle control. Moreover, the antinociceptive effect of l-THP was prevented by D1R antagonist SCH23390 or D2R agonist quinpirole; meanwhile, the hypnotic effect of l-THP was blocked by quinpirole rather than by SCH23390. Immunohistochemistry demonstrated that l-THP inhibited c-Fos overexpression induced by PSNL in the cingulate cortex and the periaqueductal gray.

CONCLUSIONS

These findings indicated that l-THP exerted analgesic effects by agonism D1R and antagonism D2R, and the antagonism of D2R mediated the hypnotic effect of l-THP in PSNL mice.

Authors+Show Affiliations

Department of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, and Institutes of Brain Science, Fudan University, Shanghai, 200032, China.Department of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, and Institutes of Brain Science, Fudan University, Shanghai, 200032, China.Department of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, and Institutes of Brain Science, Fudan University, Shanghai, 200032, China.Department of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, and Institutes of Brain Science, Fudan University, Shanghai, 200032, China. quweimin@fudan.edu.cn.Department of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, and Institutes of Brain Science, Fudan University, Shanghai, 200032, China. huangzl@fudan.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31172225

Citation

Liu, Yuan-Yuan, et al. "Dopamine D1 and D2 Receptors Mediate Analgesic and Hypnotic Effects of L-tetrahydropalmatine in a Mouse Neuropathic Pain Model." Psychopharmacology, vol. 236, no. 11, 2019, pp. 3169-3182.
Liu YY, Wang TX, Zhou JC, et al. Dopamine D1 and D2 receptors mediate analgesic and hypnotic effects of l-tetrahydropalmatine in a mouse neuropathic pain model. Psychopharmacology (Berl). 2019;236(11):3169-3182.
Liu, Y. Y., Wang, T. X., Zhou, J. C., Qu, W. M., & Huang, Z. L. (2019). Dopamine D1 and D2 receptors mediate analgesic and hypnotic effects of l-tetrahydropalmatine in a mouse neuropathic pain model. Psychopharmacology, 236(11), 3169-3182. https://doi.org/10.1007/s00213-019-05275-3
Liu YY, et al. Dopamine D1 and D2 Receptors Mediate Analgesic and Hypnotic Effects of L-tetrahydropalmatine in a Mouse Neuropathic Pain Model. Psychopharmacology (Berl). 2019;236(11):3169-3182. PubMed PMID: 31172225.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dopamine D1 and D2 receptors mediate analgesic and hypnotic effects of l-tetrahydropalmatine in a mouse neuropathic pain model. AU - Liu,Yuan-Yuan, AU - Wang,Tian-Xiao, AU - Zhou,Ji-Chuan, AU - Qu,Wei-Min, AU - Huang,Zhi-Li, Y1 - 2019/06/06/ PY - 2019/01/16/received PY - 2019/05/10/accepted PY - 2019/6/7/pubmed PY - 2020/1/29/medline PY - 2019/6/8/entrez KW - Dopamine receptor KW - Levo-tetrahydropalmatine KW - Neuropathic pain KW - Sleep disturbance KW - c-Fos SP - 3169 EP - 3182 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 236 IS - 11 N2 - RATIONALE: Levo-tetrahydropalmatine (l-THP), an active ingredient of Corydalis yanhusuo, has been reported to be a partial agonist for dopamine D1 receptors (D1R) and an antagonist for D2R. Although it has been safely used clinically in China for decades as an analgesic with sedative/hypnotic properties, there are few studies that address the mechanisms by which l-THP exerts its beneficial effects in chronic pain-induced sleep disturbance. OBJECTIVES: To investigate the effects and mechanisms of l-THP on sleep disturbance in a neuropathic pain-like condition. METHODS: A mouse model of chronic neuropathic pain induced by partial sciatic nerve ligation (PSNL) was employed. The antinociceptive and hypnotic effects of l-THP were evaluated by measurement of mechanical allodynia, thermal hyperalgesia, and electroencephalogram (EEG) recordings in PSNL mice. Pharmacological approaches and c-Fos expression were used to clarify the mechanisms of l-THP. RESULTS: Intraperitoneal injection of l-THP at 5 and 10 mg/kg not only significantly increased the mechanical threshold by 134.4% and 174.8%, and prolonged the thermal latency by 49.4% and 69.2%, but also increased non-rapid eye movement sleep by 17.5% and 29.6%, and decreased sleep fragmentation in PSNL mice, compared with the vehicle control. Moreover, the antinociceptive effect of l-THP was prevented by D1R antagonist SCH23390 or D2R agonist quinpirole; meanwhile, the hypnotic effect of l-THP was blocked by quinpirole rather than by SCH23390. Immunohistochemistry demonstrated that l-THP inhibited c-Fos overexpression induced by PSNL in the cingulate cortex and the periaqueductal gray. CONCLUSIONS: These findings indicated that l-THP exerted analgesic effects by agonism D1R and antagonism D2R, and the antagonism of D2R mediated the hypnotic effect of l-THP in PSNL mice. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/31172225/Dopamine_D1_and_D2_receptors_mediate_analgesic_and_hypnotic_effects_of_l_tetrahydropalmatine_in_a_mouse_neuropathic_pain_model_ L2 - https://dx.doi.org/10.1007/s00213-019-05275-3 DB - PRIME DP - Unbound Medicine ER -