Dual effects of dextromethorphan on cocaine-induced conditioned place preference in mice.
Dextromethorphan (DM) at supra-antitussive doses might produce psychotomimetic effects in humans. In order to understand the underlying mechanisms responsible for the behavior induced by DM, we examined the effects of DM on cocaine-induced conditioned place preference (CPP) and locomotor pattern in mice, and Fos-related antigen immunoreactivity (FRA-IR) in the striatal complex (nucleus accumbens and striatum) of the mouse brain. The effects of DM (20 and 40 mg/kg, i.p.) on the CPP for 2.5, 5, 10, and 20 mg cocaine/kg, i.p. were assessed. Pretreatment with DM dose-dependently decreased the CPP for 20 mg cocaine/kg. Similarly, pretreatment with DM appeared to reduce the CPP for 10 mg cocaine/kg, but increase the CPP for 5 mg cocaine/kg. This finding was more pronounced for 2.5 mg cocaine/kg; DM significantly increased the CPP for 2.5 mg cocaine/kg in a dose-related manner. Furthermore, these results were correlated with alterations in the locomotor pattern (marginal activity) and FRA-IR in the striatal complex. Thus, our results suggest that DM exhibits a biphasic effect on the cocaine-induced CPP and locomotor pattern.
Jhoo
W K
WK
Section of Pharmacology and Toxicology, Department of Pharmacy, College of Pharmacy, Korea Institute of Drug Abuse, Kangwon National University, Chunchon, South Korea.
Shin
E J
EJ
Lee
Y H
YH
Cheon
M A
MA
Oh
K W
KW
Kang
S Y
SY
Lee
C
C
Yi
B C
BC
Kim
H C
HC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology; D003213:Conditioning, Psychological / Q000187:drug effects*; D003915:Dextromethorphan / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009714:Nucleus Accumbens / Q000737:chemistry / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis
D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016760:Proto-Oncogene Proteins c-fos; D003915:Dextromethorphan; D003042:Cocaine