Dextromethorphan affects cocaine-mediated behavioral pattern in parallel with a long-lasting Fos-related antigen-immunoreactivity.
In order to understand the underlying mechanisms responsible for the behaviors mediated by dextromethorphan (DM), we examined the effects of DM on locomotor activity and locomotor patterns in mice, and Fos-related antigen immunoreactivity (FRA-IR) of mouse brain following repeated administration of cocaine. Combined treatments (30 min prior to each cocaine administration) with DM dose-dependently decreased locomotor activity for high doses of cocaine (20 mg/kg, i.p./day x 7). DM combinations did not significantly affect hyperactivity for 10 mg cocaine/kg, i.p./day x 7. In contrast, combined treatments with DM increased the locomotor activity for 5 mg cocaine/kg, i.p./day x 7. These results were consistent with alterations in marginal activity. Repeated administration with cocaine or DM increased FRA-IR in the nucleus accumbens (NAc) and striatum which lasted for at least 7 days. Our results suggest that DM exhibits biphasic effects on the locomotor stimulation induced by cocaine, and that locomotor activities are in parallel with FRA-IR of the striatal complex. However, the role of FRA-IR regulated by DM or/and cocaine remains to be further determined.
Kim
H C
HC
Department of Pharmacy, College of Pharmacy, Korea Institute of Drug Abuse, Kangwon National University, Chunchon, South Korea. kimhc@cc.kangwon.ac.kr
Bing
G
G
Shin
E J
EJ
Jhoo
H S
HS
Cheon
M A
MA
Lee
S H
SH
Choi
K H
KH
Kim
J I
JI
Jhoo
W K
WK
D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003915:Dextromethorphan / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*
D000996:Antitussive Agents; D016760:Proto-Oncogene Proteins c-fos; D003915:Dextromethorphan; D003042:Cocaine