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The discriminative stimulus effects of nitrous oxide in B6SJLF1/J mice
Author(s) -
Richardson Kellianne J,
Shelton Keith L
Publication year - 2013
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.27.1_supplement.658.9
Subject(s) - nmda receptor , chemistry , dizocilpine , pharmacology , nitrous oxide , isoflurane , antagonism , antagonist , stimulus control , receptor , anesthesia , medicine , biochemistry , nicotine , organic chemistry
The abuse‐related CNS effects of nitrous oxide (N 2 O) are poorly understood. In vitro data suggests that N 2 O alters the function of NMDA and GABA A receptors, amongst others. Our goal was to assess the neurotransmitter systems responsible for producing the intoxicating effects of N 2 O using drug discrimination. Twenty‐four mice were trained to discriminate 10 min of exposure to 60% N 2 O/40% O 2 versus 100% O 2 in daily 5 min operant sessions. Mice acquired the discrimination in an average of 38 days. N 2 O produced concentration‐dependent substitution for the training concentration. Full substitution required 7 min of 60% N 2 O exposure but the offset of stimulus effects N 2 O following the cessation of exposure was more rapid. In substitution studies the NMDA channel blocker MK‐801 produced up to 49% N 2 O lever‐selection at 0.56 mg/kg. While MK‐801 failed to produce more than partial substitution, an intermediate dose of 0.17 mg/kg MK‐801 significantly shifted the N 2 O concentration‐effect curve to the left. The competitive NMDA antagonist CGS 19755 and the positive GABA A modulator midazolam failed to substitute for N 2 O. Volatile anesthetic vapors methoxyflurane and isoflurane partially substituted for N 2 O. These data suggest the subjective stimulus properties of N 2 O may be partially mediated by NMDA antagonism but other receptor systems not yet examined are probably also involved. Supported by NIDA grant RO1‐DA020553.