The effects of over-expression of neuropeptide FF receptor subtype NPFFR2 on nociception and morphine antinociceptive effects

• Main Authors: Sheng Chin Kao, 高聖欽
• Other Authors: J. C. Chen
• Format: Others
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/02434147733031872858

碩士 === 長庚大學 === 臨床醫學研究所 === 100 === It has been proposed that activation of ”anti-opioid” systems during the administration of opioids may be involved in the development of opioid tolerance and dependence. The neuropeptide FF (NPFF) system has been implicated as an anti-opioid system and plays a role in modulating nociception, morphine antinociception and dependence. Two receptor subtypes, namely NPFFR1 and NPFFR2, have been identified for NPFF, but their respective role in these processes remains uncertain. In the present study, the specific role of NPFFR2 was investigated using two strains of transgenic (Tg) mice, namely C57BL/6C-Tg(Npffr2)Dyj1 (Tg2217) and C57BL/6C-Tg(Npffr2)Dyj2 (Tg2324), over-expressing NPFFR2 in the mouse central nervous system (CNS) in different extent. The expression of NPFFR2 in the spinal cord is higher in the Tg2217 strain than the Tg2324 strain, while the expression in the brain is higher in the Tg2324 strain than the Tg2217 strain. Both strains of Tg mice, especially the Tg2324 mice, exhibit increased sensitivity to thermal noxious stimuli in the hot plate test as compared to the wild type (WT) mice, while analgesic effect to acute morphine (12.5mg/kg, s.c.) is similar to the WT. The development of tolerance to morphine antinociception after chronic morphine treatment (12.5mg/kg, s.c.; twice daily × 5 days) is significantly attenuated in Tg2324 mice as compared to WT mice. The withdrawal behaviors and signs are heterogeneously regulated in the Tg mice. Compared to the WT mice, weight loss and wet-dog shake are attenuated in the Tg2217 and Tg2324 mice, respectively. Jumping behavior is attenuated in the Tg2217 but precipitated in the Tg2324 strain. Our results suggest that NPFFR2 is involved in the modulation of nociception, morphine tolerance and dependence, depending on their specific location in the CNS and relative extent of activity.