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The discriminative stimulus effects of nitrous oxidea
Author(s) -
Richardson Kellianne J,
Slavova-Hernandez Galina,
Shelton Keith L.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.660.14
Subject(s) - nmda receptor , stimulus control , pharmacology , stimulus (psychology) , dizocilpine , ketamine , nitrous oxide , antagonist , hallucinogen , neuroscience , chemistry , glutamate receptor , psychology , receptor , anesthesia , medicine , biochemistry , cognitive psychology , nicotine
Despite both widespread clinical use and a long history of abuse, there is a limited understanding of the CNS actions of the anesthetic gas nitrous oxide (N 2 O). In vitro data has shown that N 2 O oxide alters the function of NMDA and GABA A receptors, amongst others. Our overarching goal was to use drug discrimination to assess the neurotransmitter systems responsible for producing the intoxicating, subjective stimulus effects of N 2 O. Sixteen male B6SJLF1/J mice were trained to discriminate 10 min of exposure to 60% inhaled N 2 O/40% O 2 versus 100% O 2 in daily 5‐min operant sessions. Subsequently substitution tests with other compounds were conducted. We hypothesized that if the discriminative stimulus effects of N 2 O are mediated by NMDA antagonism, drugs which attenuate NMDA receptor function would substitute for N 2 O. Thus far the NMDA channel blockers ketamine and MK‐801 have shown partial substitution for N 2 O. Of 8 mice tested with ketamine, 5 fully substituted at 7 or 10 mg/kg. Of 6 mice thus far tested with MK‐801, 4 fully substituted at 0.1– 0.3 mg/kg. The NMDA competitive antagonist CGS 19755 did not substitute for N 2 O, producing exclusively vehicle appropriate responding in 4 of 5 mice. These results suggest the subjective stimulus properties of N 2 O overlap with those of noncompetitive NMDA antagonists, suggesting common underlying mechanisms of action. Supported by NIDA grant RO1‐DA020553.