Ventilatory response of peripheral chemoreceptors to hypercapnia during exercise above the respiratory compensation point.

Peripheral hypercapnic chemosensitivity (PHC) is assessed as the change in ventilation in response to a rapid change in carbon dioxide pressures (Pco2). The increase in chemoresponse from rest to subrespiratory compensation point (RCP) exercise intensities is well-defined but less clear at intensities above the RCP when changes in known ventilatory stimulants occur. Twenty healthy subjects (n = 10 females) completed a maximal exercise test on 1 day, and on a subsequent day, transient hypercapnia was used to test PHC at multiple exercise stages. The transient hypercapnia involved two breaths of 10% CO2 repeated five times during each of the following: sitting at rest on the cycle ergometer, cycling at 40% wmax, cycling at 85% Wmax, at rest on the cycle ergometer immediately following the 85% stage, and cycling at 40% Wmax again following the postexercise rest. The PHC was not different across exercise intensities (0.98 ± 0.37 vs. 0.91 ± 0.39 vs. 0.92 ± 0.42 L·min-1·mmHg-1 for first 40% wmax, 85% wmax and second 40% Wmax, respectively (P = 0.45). There were no differences in PHC between presupra-RCP exercise rest and postsupra-RCP exercise rest (0.52 ± 0.23 vs. 0.53 ± 0.24 L·min-1·mmHg-1, P = 0.8003). Using a repeated-measures correlation to account for within-participant changes, there was a significant relationship between the end-tidal Pco2 and PHC for the 85% intensity (r = 0.5, P < 0.0001) when end-tidal Pco2 was dynamic between the trials. We conclude that the physiological changes (e.g., metabolic milieu and temperature) produced with supra-RCP exercise do not further augment PHC, and that the prestimulus end-tidal Pco2 modulates the PHC.NEW & NOTEWORTHY Exercise at intensities above the respiratory compensation point did not further augment peripheral hypercapnic chemosensitivity (PHC). Moreover, the PHC was not different during a preexercise resting state compared with rest immediately after intense exercise. The lack of differences across both comparisons suggests that exercise itself appears to sensitize the PHC.

Peripheral hypercapnic chemosensitivity at rest and progressive exercise intensities in males and females.

Peripheral hypercapnic chemosensitivity (PHC) is the ventilatory response to hypercapnia and is enhanced with acute whole body exercise. However, little is known about the mechanism(s) responsible for the exercise-related increase in PHC and if progressive exercise leads to further augmentation. We hypothesized that unloaded cycle exercise (0 W) would increase PHC but progressively increasing the intensity would not further augment the response. Twenty healthy subjects completed two testing days. Day 1 was a maximal exercise test on a cycle ergometer to determine peak power output (Wmax). Day 2 consisted of six 12-min stages: 1) rest on chair, 2) rest on bike, 3) 0 W unloaded cycling, 4) 25% Wmax, 5) 50% Wmax, and 6) ∼70% Wmax with ∼10 min of rest between each exercise stage. In each stage, PHC was assessed via two breaths of 10% CO2 (∼21% O2) repeated five times with ∼45 s between each to ensure end-tidal CO2 ([Formula: see text]) and ventilation returned to baseline. Prestimulus [Formula: see text] was not different between rest and unloaded cycling (P = 0.478). There was a significant increase in PHC between seated rest and 25% Wmax (0.71 ± 0.37 vs. 1.03 ± 0.52 L·mmHg-1·min-1, respectively, P = 0.0006) and between seated rest and unloaded cycling (0.71 ± 0.37 vs. 1.04 ± 0.4 L·mmHg-1·min-1, respectively, P = 0.0017). There was no effect of exercise intensity on PHC (1.03 ± 0.52 vs. 0.95 ± 0.58 vs. 1.01 ± 0.65 L·mmHg-1·min-1 for 25, 50, and 70% Wmax, P = 0.44). The increased PHC response from seated rest to unloaded and 25% Wmax, but no effect of exercise intensity suggests a possible feedforward/feedback mechanism causing increased PHC sensitivity through the act of cycling.NEW & NOTEWORTHY Unloaded exercise significantly increased the peripheral hypercapnic ventilatory response (HCVR) compared with rest. However, increases in exercise intensity did not further augment peripheral HCVR. Males had a greater peripheral HCVR compared with females, but there was no interaction between sex and intensity. The lack of sex interactions suggests the mechanism augmenting the peripheral HCVR with exercise is independent of sex. The increase in peripheral HCVR with exercise is likely due to central command.

Estradiol administration increases anxiety-like behavior following chronic escalating morphine administration in hormone-replaced ovariectomized female rats.

Withdrawal from opioids can induce a state of anxiety and irritability. This negative state can facilitate continued drug taking, as the administration of opioids can alleviate unpleasant symptoms associated with acute and protracted withdrawal. It is, therefore, of interest to investigate factors that can contribute to the severity of anxiety during periods of abstinence. One such factor is the fluctuation of ovarian hormones. Evidence from a non-opioid drug indicates that estradiol increases, while progesterone decreases anxiety during withdrawal. However, no work has yet studied how ovarian hormones might influence the severity of anxiety during withdrawal from opioids. To explore this, we ovariectomized female rats and provided a four-day repeating cycle of ovarian hormone administration (Day 1: estradiol, Day 2: estradiol, Day 3: progesterone, Day 4: peanut oil). Male rats were given sham surgeries and administered peanut oil daily in lieu of hormone replacement. All rats received twice daily injections of morphine (or 0.9 % saline) for 10 days total at a dose that doubled every two days (2.5 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg, 40 mg/kg). Rats underwent spontaneous withdrawal and were tested for anxiety-like behaviors 12 and 108 h after the last morphine treatment. At 12 h, morphine-withdrawn female rats treated with estradiol on the day of testing displayed significantly more anxiety-like behavior in light-dark box testing than female morphine-withdrawn and (marginally) male morphine-withdrawn rats receiving vehicle that day. Somatic withdrawal behaviors (wet dog shakes, head shakes, writhing) were also taken every 12 h through 108 h. We found no meaningful contribution of sex or hormones for these measures. This study is the first of its kind to provide evidence that ovarian hormones influence anxiety-like behavior during morphine withdrawal.

Interoceptive hunger, eating attitudes and beliefs.

Interoceptive individual differences have garnered interest because of their relationship with mental health. One type of individual difference that has received little attention is variability in the sensation/s that are understood to mean a particular interoceptive state, something that may be especially relevant for hunger. We examined if interoceptive hunger is multidimensional and idiosyncratic, if it is reliable, and if it is linked to dysfunctional eating and beliefs about the causes of hunger. Participants completed a survey just before a main meal, with most retested around 1 month later. We found that interoceptive hunger has 11 dimensions, and while people differ considerably in their combinations of interoceptive hungers, these represent only 4% of all possible permutations. Hunger reports were reliable. We found relationships between variability in hunger interoception and dysfunctional eating, especially for uncontrolled eating. We also found that hunger beliefs were in some cases strongly related to aspects of hunger interoception. The implications of these findings are discussed.

The development of interoceptive hunger signals.

Hunger is often reported when people experience certain internal sensations (e.g., fatigue) or when they anticipate that a food will be good to eat. The latter results from associative learning, while the former was thought to signal an energy deficit. However, energy-deficit models of hunger are not well supported, so if interoceptive hungers are not "fuel gauges," what are they? We examined an alternate perspective, where internal states signaling hunger, which are quite diverse, are learned during childhood. A basic prediction from this idea is offspring-caregiver similarity, which should be evident if caregivers teach their child the meaning of internal hunger cues. We tested 111 university student offspring-primary caregiver pairs, by having them complete a survey about their internal hunger states, alongside other information that may moderate this relationship (i.e., gender, body mass index, eating attitudes, and beliefs about hunger). We observed substantial similarity between offspring-caregiver pairs (Cohen's ds from 0.33 to 1.55), with the main moderator being beliefs about an energy-needs model of hunger, which tended to increase similarity. We discuss whether these findings may also reflect heritable influences, the form that any learning might take, and the implications for child feeding practices.