Individual differences in rat sensitivity to CO2

Abstract

Feelings of fear, anxiety, dyspnea and panic when inhaling carbon dioxide (CO2) are variable among humans, in part due to differences in CO2 sensitivity. Rat aversion to CO2 consistently varies between individuals; this variation in aversion may reflect CO2 sensitivity, but other personality traits could also account for individual differences in aversion. The aims of this study were to 1) assess the stability of individual differences in rat aversion to CO2, 2) determine if individual differences in sweet reward motivation are associated with variation in aversion to CO2, and 3) assess whether variation in aversion to CO2 is related to individual differences in motivation to approach gains (promotion focus) or maintain safety (prevention focus). Twelve female Sprague Dawley rats were exposed multiple times at three different ages (3, 9 and 16 months old) to CO2 in approach-avoidance testing to assess motivation to avoid CO2 against motivation to gain sweet rewards. Rats were also tested for motivation to find hidden sweet rewards, and for their motivation to approach rewards or darkness. Tolerance to CO2 increased with repeated exposures and was higher at older ages. Individual differences in aversion to CO2 were highly repeatable but unrelated to motivation for sweet rewards or the strength of promotion and prevention focus. These results indicate that individual differences in aversion to CO2 reflect variation in CO2 sensitivity.

Fig 1. Experimental apparatus.

a) Approach-avoidance apparatus used to assess aversion to CO₂. Measurements were: The top cage 20 cm x 50 cm x 40 cm, bottom cage 20 cm x 45 cm x 24 cm, connecting tube 10 cm diameter x 45 cm long, and plastic sliding door 10 cm x 10 cm. b) Modified approach-avoidance apparatus used to evaluate motivation for sweet rewards, the test cage measured 20 cm x 45 cm x 24 cm and the ice cube trays 32 cm x 12 cm x 4 cm. c) Modified open field arena used to assess promotion and prevention motivation focus, the arena was made of white acrylic glass (100 cm x 100 cm x 61 cm) and contained two smaller acrylic glass boxes (10 cm3) placed against the center of two adjacent walls of the arena (treat and dark locations).

Fig 2. Experiments timeline.

Order of testing across the three experiments (i.e. aversion to CO2, sweet reward motivation and regulatory focus). In all three experiments rats were trained, retrained or tested every weekday but not on weekends.

Fig 3. Effect of repeated exposures in aversion to CO₂ at 3, 9 and 16 months of age.

Individuals are represented by solid lines; the color identifying individuals are consistent across ages. Dashed lines represent the change in CO₂ tolerance with repeated exposures within each age.

Fig 4. Individual differences in aversion to CO₂, arranged from the least to the most tolerant rat.

Bigger and solid shapes indicate the mean and error bars show the standard error for each individual rat within each age. Smaller and transparent shapes represent observation from each rat at each age. Each age is presented with a different shape (circles: 3 months, triangles: 9 months, squares: 16 months) and each color represents an individual rat.

Fig 5. Individual differences in sweet reward motivation.

Individual rat (n = 11) mean (± SE) a) searching time, and b) rewards consumed, across three sweet reward motivation trials. Rat identity follows that shown in Fig 4.

Fig 6. Relationship between aversion to CO₂ and sweet reward motivation.

Each dot represents an individual rat’s point estimate (obtained from the BLUPs of the random effects of 1000 simulations) of aversion to CO₂ and their average a) searching time, and b) rewards consumed, from the sweet reward motivation trials (n = 11).

Fig 7

Regulatory focus consistency for individual rats (n = 11) tested in two trials; results are shown separately for measures of a) treat location time (promotion motivation), and b) dark location time (prevention motivation). Rat identity is given by a number following the order presented in Fig 4.