PMID- 10485964
OWN - NLM
STAT- MEDLINE
DCOM- 19991013
LR  - 20191210
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 146
IP  - 1
DP  - 1999 Sep 1
TI  - Evaluation of the reinforcing properties and phencyclidine-like discriminative 
      stimulus effects of dextromethorphan and dextrorphan in rats and rhesus monkeys.
PG  - 49-59
AB  - RATIONALE: Dextromethorphan (DXM) and its metabolite, dextrorphan (DXO) have 
      neuroprotective and anticonvulsant properties through their activity as 
      N-methyl-D-aspartate (NMDA) receptor channel blockers. Based on this receptor 
      activity, coupled with reports of DXM abuse, both were evaluated for abuse 
      potential and phencyclidine (PCP)-like behavioral effects in two animal models. 
      OBJECTIVES AND METHODS: The discriminative stimulus properties of DXO and DXM 
      were tested in rats (3-56 mg/kg DXM, i.p. and 2.2-40.9 mg/kg DXO, i.p.) and 
      rhesus monkeys (0.3-10 mg/kg DXM, i.m. and 0.25-8.0 mg/kg DXO, i. m.) trained to 
      discriminate PCP from saline using a standard two-lever drug-discrimination 
      paradigm under a fixed-ratio (FR) schedule of food reinforcement. In a second set 
      of experiments, i.v. self-administration of DXO (10-100 microg/kg/infusion) and 
      DXM (10-1000 microg/kg/infusion) were tested under a FR schedule of reinforcement 
      in monkeys trained to lever press for infusions of PCP during daily 1-h sessions. 
      RESULTS: In rats, both DXM and DXO produced a dose-dependent substitution for 
      PCP. When tested in monkeys, DXM yielded partial (1 monkey) and full (2 monkeys) 
      substitution for PCP, while DXO substituted fully for PCP in all four subjects 
      tested. In the self-administration study, in five of the six subjects, at least 
      one dose of DXM served as a positive reinforcer, maintaining infusion rates above 
      those for saline. For DXO, at least one dose maintained infusion numbers well 
      above mean saline infusion numbers in all subjects. CONCLUSIONS: Taken together, 
      these data show that DXM has some PCP-like effects in rats and monkeys, but that 
      they are more reliably produced by its metabolite, DXO. Thus, high doses of DXM 
      may have some PCP-like abuse potential in humans but this potential may be 
      associated with, or enhanced by, metabolism of DXM to DXO.
FAU - Nicholson, K L
AU  - Nicholson KL
AD  - Department of Pharmacology and Toxicology, Medical College of Virginia, Box 
      980310, Virginia Commonwealth University, Richmond, VA 23298-0310, USA,
FAU - Hayes, B A
AU  - Hayes BA
FAU - Balster, R L
AU  - Balster RL
LA  - eng
GR  - DA-01442/DA/NIDA NIH HHS/United States
GR  - DA-07027/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Antitussive Agents)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 7355X3ROTS (Dextromethorphan)
RN  - J1DOI7UV76 (Phencyclidine)
SB  - IM
MH  - Animals
MH  - Antitussive Agents/*pharmacology
MH  - Dextromethorphan/metabolism/*pharmacology
MH  - Discrimination Learning/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Macaca mulatta
MH  - Male
MH  - Phencyclidine/*pharmacology
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
MH  - *Reinforcement, Psychology
MH  - Self Administration
EDAT- 1999/09/15 00:00
MHDA- 1999/09/15 00:01
CRDT- 1999/09/15 00:00
PHST- 1999/09/15 00:00 [pubmed]
PHST- 1999/09/15 00:01 [medline]
PHST- 1999/09/15 00:00 [entrez]
AID - 91460049.213 [pii]
AID - 10.1007/s002130051087 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 1999 Sep 1;146(1):49-59. doi: 10.1007/s002130051087.