Morphine withdrawal affects both delayed-escape behaviour in Morris water maze and hippocampal NR2A/2B expression ratio.
Repeated low-dose morphine treatment facilitates delayed-escape behaviour of hippocampus-dependent Morris water maze and morphine withdrawal influences hippocampal NMDA receptor-dependent synaptic plasticity. Here, we examined whether and how morphine withdrawal influenced delayed-escape behaviour and NR2A/2B expression ratio of hippocampal synaptosomes. We found that both delayed-escape behaviour and NR2A/2B expression ratio showed an inverted-U curve and peaked on 4-day withdrawal during a 20-day withdrawal period. Furthermore, treatment of the glucocorticoid receptor antagonist RU38486 for 3 days reduced delayed-escape behaviour and NR2A/2B ratio on 4-day withdrawal to a level similar to those of 18-h withdrawal. In contrast, elevated-platform stress enabled delayed-escape behaviour of 18-h withdrawal to a higher level similar to that of 4-day withdrawal, but had no significant effect on the NR2A/2B ratio. Similar behavioural effects were also found after intrahippocampal infusions of the NMDAR antagonist AP-5 or NR2B-containing NMDAR antagonist Ro25-6981 for 3 days. These findings suggest that delayed-escape behaviour enabled by repeated low-dose morphine treatment may be a useful and simple rat model for studying addictive memories to be retrieved by stress exposure.
Dong
Zhifang
Z
Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, PR China.
Zhong
Weixia
W
Tian
Meng
M
Han
Huili
H
Mao
Rongrong
R
Cao
Jun
J
Sui
Nan
N
Xu
Tianle
T
Luo
Jianhong
J
Xu
Lin
L
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009020:Morphine / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; C056639:2-amino-5-phosphopentanoic acid; D009020:Morphine; D014633:Valine