NMDA receptor in nucleus accumbens is implicated in morphine withdrawal in rats.
The purpose of the present study is to elucidate whether ketamine, a non-competitive antagonist of the NMDA receptor, can suppress the morphine withdrawal syndrome in rats at a dose without affecting motor functions and to identify its site of action in the central nervous system. Rats were made dependent on morphine by multiple injections of morphine hydrochloride for 5 days. They were then given ketamine at the following doses and routes of administration: (a) intraperitoneal (i.p.) injections (2-16 mg/kg), (b) intracerebroventricular (i.c.v.) injections (4-100 microg), and (c) intra-nucleus accumbens (NAc) or intra-amygdalar microinjections (0.4-10 microg). Naloxone HCl (1 mg/kg, i.p.) was administered 3 h after the last ketamine injection to precipitate withdrawal syndrome, which was scored within a period of 30 min. Results showed that some of the precipitated withdrawal signs were dose-dependently suppressed by repeated injections of ketamine at 8 and 16 mg/kg, i.p. or 100 microg, i.c.v. Dose-dependent suppression was observed by repeated microinjections (0.4-10 microg) of ketamine to NAc, but not to amygdala. These results indicate that the NMDA receptor antagonist ketamine has the ability to suppress morphine withdrawal syndrome in experimental settings without motor interference, and NAc could be the critical CNS site mediating such effect.
Ji
Dong
D
Neuroscience Research Institute, Peking University, Key Laboratory for Neuroscience, Beijing, PR China.
Sui
Zi-Ye
ZY
Ma
Yao-Ying
YY
Luo
Fei
F
Cui
Cai-Lian
CL
Han
Ji-Sheng
JS
D000679:Amygdala; D000701:Analgesics, Opioid / Q000009:adverse effects*; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007267:Injections; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007649:Ketamine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000503:physiopathology
D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D009270:Naloxone; D007649:Ketamine; D009020:Morphine