1. Post-treatment of dextromethorphan reverses morphine effect on conditioned place preference in rats.
- Author
-
Lue WM, Huang EY, Yang SN, Wong CS, and Tao PL
- Subjects
- Animals, Brain metabolism, Brain physiopathology, Brain Chemistry physiology, Conditioning, Psychological physiology, Corpus Striatum drug effects, Corpus Striatum metabolism, Dextromethorphan therapeutic use, Dopamine metabolism, Excitatory Amino Acid Antagonists pharmacology, Excitatory Amino Acid Antagonists therapeutic use, Male, Morphine Dependence metabolism, Morphine Dependence physiopathology, Narcotics adverse effects, Neural Pathways drug effects, Neural Pathways metabolism, Neural Pathways physiopathology, Nucleus Accumbens drug effects, Nucleus Accumbens metabolism, Nucleus Accumbens physiopathology, Prefrontal Cortex drug effects, Prefrontal Cortex metabolism, Rats, Rats, Sprague-Dawley, Reinforcement, Psychology, Synaptic Transmission drug effects, Synaptic Transmission physiology, Ventral Tegmental Area drug effects, Ventral Tegmental Area metabolism, Ventral Tegmental Area physiopathology, Brain drug effects, Brain Chemistry drug effects, Conditioning, Psychological drug effects, Dextromethorphan pharmacology, Morphine adverse effects, Morphine Dependence drug therapy
- Abstract
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 Rats were injected and conditioned with morphine for 6 days and then withdrawn from morphine for 4 days and treated with saline or DM during this period.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.
- Published
- 2007
- Full Text
- View/download PDF