Comparative effects of dextromethorphan and dextrorphan on morphine, methamphetamine, and nicotine self-administration in rats.
The effects of dextromethorphan and its metabolite dextrorphan on morphine, methamphetamine and nicotine self-administration and on responding for a nondrug reinforcer (water) were assessed in rats. Both dextromethorphan and dextrorphan decreased morphine self-administration at 10-30 mg/kg, s.c., decreased methamphetamine self-administration at 20 and 30 mg/kg, s.c., and decreased nicotine self-administration at 5-30 mg/kg, s.c.; doses of both drugs less than 40 mg/kg, s.c. did not affect responding for water. The equal potencies of dextromethorphan and dextrorphan suggest mediation of these effects by a non-NMDA receptor mechanism, possibly involving blockade of alpha3beta4 nicotinic receptors. The results also suggest that dextromethorphan should be tested extensively as a potential treatment for diverse populations of drug-abusing patients.
Glick
S D
SD
Center for Neuropharmacology and Neuroscience, Albany Medical College (MC-136), 47 New Scotland Avenue, Albany, NY 12208, USA. glicks@mail.amc.edu
Maisonneuve
I M
IM
Dickinson
H A
HA
Kitchen
B A
BA
D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D003915:Dextromethorphan / Q000494:pharmacology*; D003917:Dextrorphan / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D005731:Ganglionic Stimulants / Q000008:administration & dosage; D008694:Methamphetamine / Q000008:administration & dosage*; D009020:Morphine / Q000008:administration & dosage*; D009538:Nicotine / Q000008:administration & dosage*; D051381:Rats; D020318:Rats, Long-Evans; D012646:Self Administration
D000701:Analgesics, Opioid; D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D005731:Ganglionic Stimulants; D003917:Dextrorphan; D008694:Methamphetamine; D009538:Nicotine; D003915:Dextromethorphan; D009020:Morphine