Different Patterns of Respiration in Rat Lines Selectively Bred for High or Low Anxiety

Abstract

In humans, there is unequivocal evidence of an association between anxiety states and altered respiratory function. Despite this, the link between anxiety and respiration has been poorly evaluated in experimental animals. The primary objective of the present study was to investigate the hypothesis that genetic lines of rats that differ largely in their anxiety level would display matching alterations in respiration. To reach this goal, respiration was recorded in high-anxiety behavior (HAB, n = 10) and low-anxiety behavior (LAB, n = 10) male rats using whole-body plethysmography. In resting state, respiratory rate was higher in HABs (85±2 cycles per minute, cpm) than LABs (67±2 cpm, p<0.05). During initial testing into the plethysmograph and during a restraint test, HAB rats spent less time at high-frequency sniffing compared to LAB rats. In addition, HAB rats did not habituate in terms of respiratory response to repetitive acoustic stressful stimuli. Finally, HAB rats exhibited a larger incidence of sighs during free exploration of the plethysmograph and under stress conditions. We conclude that: i) HAB rats showed respiratory changes (elevated resting respiratory rate, reduced sniffing in novel environment, increased incidence of sighs, and no habituation of the respiratory response to repetitive stimuli) that resemble those observed in anxious and panic patients, and ii) respiratory patterns may represent a promising way for assessing anxiety states in preclinical studies.

Long-lasting bradypnea induced by repeated social defeat

“…Clinical studies have shown that panic disorder, characterized by acute and unexpected anxiety attacks and substantial anxiety over the possibility of experiencing further attacks, is associated with symptoms including palpitations, shortness of breath, sweating, and hyperventilation (1). In addition, high levels of anxiety-related behavior in rats are associated with elevation of the resting respiratory rate (9). The respiratory rate also decreases during certain specific responses to stress, for instance during freezing behavior in the rat, when it is associated with ultrasonic vocalizations (19).…”

Amygdala mediates respiratory responses to sudden arousing stimuli and to restraint stress in rats

“…These responses are likely linked with animals' anxiety state, as they are sensitive to anxiolytic drug diazepam (23) and are significantly increased in rats with induced high-anxiety behavior (32). There are also substantial differences in respiratory pattern between rats bred for low-anxiety behavior compared with animals bred for high-anxiety behavior (5). The brains substrate of the anxiety-related respiratory responses is poorly understood.…”

Autonomic changes induced by provocative motion in rats bred for high (HAB) and low (LAB) anxiety-related behavior: Paradoxical responses in LAB animals

“…(and bradycardia) response in LAB compared to HAB and NAB is due to an increased sensitivity in the vestibular-thermoregulatory/cardiovascular pathways that are psychogenetically selected by the elevated plus-maze test. Previous studies [5,6] have identified phenotypic differences in the cardio-respiratory control in LAB compared to HAB/NAB animals, and this study identifies a novel unpredicted phenotypic difference. In addition, it is also possible that selection of the LAB phenotype included selection for animals with enhanced vestibular sensitivity.…”

“…other physiological parameter such as an increased hypothalamic expression and release of vasopressin [32], differences in pain sensitivity [22], increased hormonal response of the HPA axis to novelty [26] and elevated frequency of breathing [5] in HAB rats.…”