Fig 1.
Calorimetric Assessment During an Initial 60% N2O Administration Distinguishes Initially Sensitive from Initially Insensitive Rats.
Thermal profiles ± pointwise SE (shaded areas) of rats designated as initially sensitive (IS, n = 16) and initially insensitive (II, n = 16) based upon a N2O screening test of n = 189 candidates. A: Core temperature (Tc); B: heat production (HP); C: dry heat loss (DHL), and D: evaporative heat loss (EHL). HP data between 0 and 12 min are not depicted because it has been documented that the initiation of N2O delivery can cause a transient artifactual effect on HP [14].
Fig 2.
N2O Self-Administration Data for Initially Sensitive and Initially Insensitive Rats.
Ternary diagram depicting the centered geometric mean proportions of time spent in each chamber for each of the eight 44-h dyads during N2O availability. The numbers 1–8 depicted in the figure represent the sequential order of self-administration dyads. Circled numbers represent dyads for initially insensitive rats (II, n = 16) while uncircled numbers represent dyads for the initially sensitive rats (IS, n = 16). The position of each point relative to the three color-coded axes indicates the proportion of time spent in the central tub (black), control gas chamber (red), and 60% N2O chamber (blue) during a 44-h dyad.
Fig 3.
Statistical Comparison of the N2O Preference Ratio for Initially Sensitive and Initially Insensitive Rats.
The N2O preference ratio is the ratio of time each rat spent in the N2O chamber versus the control air chamber during each dyad, and was compared between initially insensitive (II, black circles) and initially sensitive (IS, red triangles) rats using linear modeling applied to log-transformed ratios. Points represent geometric means and error bars are pointwise 95% confidence intervals. Ratio comparisons were statistically significant in each of Dyads 5–8. During Dyads 5–8, the II group’s mean N2O preference ratio was 3.68-fold higher than that of IS rats (95% CI: 1.48–9.20; p = 0.003). For Dyads 1–4, the preference ratio was 1.84 times greater than that of the IS group (95% CI: 0.80–4.40), but this difference did not reach statistical significance (p = 0.075). The group-by-dyad interactions were not statistically significant for Dyads 1–4 (p = 0.227) or for Dyads 5–8 (p = 0.343).
Fig 4.
Final Calorimetric Assessment during a 60% N2O Administration for Initially Sensitive and Initially Insensitive Rats.
A calorimetry retest conducted after the self-administration phase revealed that the IS and II groups both became frankly hyperthermic with the onset of 60% N2O administration but the magnitude was markedly greater and more persistent in the N2O self administration-prone II rats (A) due primarily to a greater HP response (B). The increases in DHL (C) and EHL (D) likely reflect a durable pharmacological effect of N2O in addition to the effect of increased body heat content to promote heat loss. The II and IS groups did not differ during the control gas session (E, F, G, H).