The discriminative stimulus effects of nitrous oxide in B6SJLF1/J mice
Kellianne J. Richardson, Keith L Shelton
The FASEB Journal April 1, 2013 DOI: 10.1096/fasebj.27.1_supplement.658.9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Drug discrimination study in mice Peer reviewed |
|---|---|
| Sample size | 24 |
| Population | Mice trained to discriminate nitrous oxide from oxygen |
| Interventions | Nitrous oxide CGS 19755 midazolam methoxyflurane isoflurane |
| Dose | 60% N2O/40% O2; MK-801 0.56 mg/kg and 0.17 mg/kg |
| Duration | Daily 5-minute operant sessions; training averaged 38 days; 10-minute exposures in discrimination training |
| Key points | Nitrous oxide produced concentration-dependent substitution for the training stimulus, with full substitution requiring 7 minutes of 60% exposure. MK-801 produced at most 49% nitrous oxide lever selection at 0.56 mg/kg and shifted the nitrous oxide concentration-effect curve left at 0.17 mg/kg, while CGS 19755 and midazolam did not substitute and methoxyflurane and isoflurane partially substituted. The authors suggest nitrous oxide's stimulus properties may be partly mediated by NMDA antagonism, with other receptor systems probably also involved. |
Abstract
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.