Dextromethorphan increases tyrosine hydroxylase mRNA in the mesencephalon of adolescent rats.
Dextromethorphan (DM), an antitussive widely available in over-the-counter, has been abused mostly in teenage groups at high doses. To examine effects of DM on the reward pathway, we injected a high dose of DM (40 mg/kg; intraperitoneally) into the adolescent rat and measured tyrosine hydroxylase (TH) mRNA by in situ hybridization in the ventral tegmental area (VTA) and the substantia nigra (SN). Remarkable increases in the level of TH mRNA were observed in the VTA and SN 2 h after DM injection. Stereotyped behavior and ataxia increased, and rearing decreased by DM administration. These results suggest that DM-induced increase in TH mRNA expression in mesencephalon contribute to the reinforcing property and the behavioral effects of DM.
Zhang
T Y
TY
Department of Pharmacology and Yonsei Brain Research Institute, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, South Korea.
Jahng
J W
JW
Kim
D G
DG
D000367:Age Factors; D000818:Animals; D003915:Dextromethorphan / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D017403:In Situ Hybridization; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019966:Substance-Related Disorders / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects* / Q000201:enzymology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000201:enzymology
D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; D003915:Dextromethorphan; D014446:Tyrosine 3-Monooxygenase