TY - JOUR
T1 - Nociceptin and the NOP receptor in aversive learning in mice
AU - Adem, Abdu
AU - Madjid, Nather
AU - Kahl, Ulrika
AU - Holst, Sarah
AU - Sadek, Bassem
AU - Sandin, Johan
AU - Terenius, Lars
AU - Ögren, Sven Ove
N1 - Funding Information:
This work was supported by the Marcus and Amalia Wallenberg Foundation (SOÖ), the Alzheimer Foundation (AF-555891) (SOÖ) AA was supported by two grants: 1. Interdisciplinary grant ( 31R024 ) from the United Arab Emirates University . 2. Faculty grant ( NP14-42 ) from the College of Medicine and Health Sciences .
Funding Information:
This work was supported by the Marcus and Amalia Wallenberg Foundation (SO?), the Alzheimer Foundation (AF-555891) (SO?) AA was supported by two grants: 1. Interdisciplinary grant (31R024) from the United Arab Emirates University. 2. Faculty grant (NP14-42) from the College of Medicine and Health Sciences.
Publisher Copyright:
© 2017 Elsevier B.V. and ECNP
PY - 2017/12
Y1 - 2017/12
N2 - The endogenous neuropeptide nociceptin (N/OFQ), which mediates its actions via the nociceptin receptor (NOP), is implicated in multiple behavioural and physiological functions. This study examined the effects of the NOP agonists N/OFQ and the synthetic agonist Ro 64–6198, the antagonists NNN and NalBzoH, as well as deletion of the Pronociceptin gene on emotional memory in mice. The animals were tested in the passive avoidance (PA) task, dependent on hippocampal and amygdala functions. N/OFQ injected intraventricularly (i.c.v.) prior to training produced a biphasic effect on PA retention; facilitation at a low dose and impairment at higher doses. Ro 64–6198 also displayed a biphasic effect with memory facilitation at lower doses and impairment at a high dose. None of the agonists influenced PA training latencies. NNN did not significantly modulate retention in the PA task but antagonized the inhibitory effects of N/OFQ. NalBzoH facilitated memory retention in a dose-dependent manner and blocked the impairing effects of N/OFQ. However, neither NNN nor NalBzoH blocked the memory-impairing effects of Ro 64–6198. Finally, the Pnoc knockout mice exhibited enhanced PA retention latencies compared to the wild type mice. The biphasic effect of the natural ligand and Ro 64–6198 and the failure of the antagonists to block the action of Ro 64–6198 indicate complexity in ligand-receptor interaction. These results indicate that brain nociceptin and its NOP has a subtle role in regulation of mechanisms of relevance for treatment of disorders with processing disturbances of aversive events e.g. Alzheimer's disease, anxiety, depression and PTSD.
AB - The endogenous neuropeptide nociceptin (N/OFQ), which mediates its actions via the nociceptin receptor (NOP), is implicated in multiple behavioural and physiological functions. This study examined the effects of the NOP agonists N/OFQ and the synthetic agonist Ro 64–6198, the antagonists NNN and NalBzoH, as well as deletion of the Pronociceptin gene on emotional memory in mice. The animals were tested in the passive avoidance (PA) task, dependent on hippocampal and amygdala functions. N/OFQ injected intraventricularly (i.c.v.) prior to training produced a biphasic effect on PA retention; facilitation at a low dose and impairment at higher doses. Ro 64–6198 also displayed a biphasic effect with memory facilitation at lower doses and impairment at a high dose. None of the agonists influenced PA training latencies. NNN did not significantly modulate retention in the PA task but antagonized the inhibitory effects of N/OFQ. NalBzoH facilitated memory retention in a dose-dependent manner and blocked the impairing effects of N/OFQ. However, neither NNN nor NalBzoH blocked the memory-impairing effects of Ro 64–6198. Finally, the Pnoc knockout mice exhibited enhanced PA retention latencies compared to the wild type mice. The biphasic effect of the natural ligand and Ro 64–6198 and the failure of the antagonists to block the action of Ro 64–6198 indicate complexity in ligand-receptor interaction. These results indicate that brain nociceptin and its NOP has a subtle role in regulation of mechanisms of relevance for treatment of disorders with processing disturbances of aversive events e.g. Alzheimer's disease, anxiety, depression and PTSD.
KW - Emotional memory
KW - Mice
KW - NOP
KW - Nociceptin
KW - Passive avoidance
KW - Ro 64–6198
UR - http://www.scopus.com/inward/record.url?scp=85032387122&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032387122&partnerID=8YFLogxK
U2 - 10.1016/j.euroneuro.2017.09.005
DO - 10.1016/j.euroneuro.2017.09.005
M3 - Article
C2 - 29102248
AN - SCOPUS:85032387122
SN - 0924-977X
VL - 27
SP - 1298
EP - 1307
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
IS - 12
ER -