Post-treatment of dextromethorphan reverses morphine effect on conditioned place preference in rats.
Previously we showed that coadministration of dextromethorphan (DM) with morphine attenuates morphine-rewarding effect. Here we further investigated if DM is effective in reversing or treating drug-seeking effect when given after subchronic morphine treatment. The conditioned place preference (CPP) test was used to investigate the rewarding and drug-seeking effects of morphine. Rats were injected and conditioned with morphine for 6 days and then withdrawn from morphine for 4 days and treated with saline or DM during this period. Subchronic morphine induced a significant place preference for the drug-paired compartment. DM treatment during the morphine withdrawal period significantly reversed the preference from the drug-paired compartment to saline-paired compartment. Both nucleus accumbens (NAc) and VTA were proven to be the sites involved in the action of DM. Behavioral sensitization occurred in both morphine group and DM treatment group determined by the locomotor activity before and after subchronic morphine treatment. The dopamine (DA) turnover rate in the NAc, dorsal striatum (DS) and medial prefrontal cortex (mPFC) was increased after subchronic morphine treatment. DM treatment reversed the increase of DA turnover rate in the NAc but not in the DS or mPFC. These data suggest that DM might have potential in the treatment of morphine addiction.
Lue
Wei-Ming
WM
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Huang
Eagle Yi-Kung
EY
Yang
San-Nan
SN
Wong
Chih-Shung
CS
Tao
Pao-Luh
PL
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003915:Dextromethorphan / Q000494:pharmacology* / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009021:Morphine Dependence / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009294:Narcotics / Q000009:adverse effects; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology
D018691:Excitatory Amino Acid Antagonists; D009294:Narcotics; D003915:Dextromethorphan; D009020:Morphine; D004298:Dopamine