Association between estrus cycle-related aggression and tidal volume variability in female Wistar rats.

Premenstrual dysphoria is characterized by symptoms such as irritability and depressed mood, present during the luteal phase of the menstrual cycle, and disappearing shortly after the onset of menstruation. Subjects with premenstrual dysphoria have previously been reported to display enhanced respiratory variability, and to experience anxiety when exposed to panicogens, such as CO2. In the present study, the possible influence of the estrus cycle and estrus cycle-related aggression on respiratory variability was investigated in female rats of the Wistar strain. The rats were subdivided into two groups: those displaying estrus cycle-related aggression, as evaluated using the resident intruder paradigm, and those not showing aggression throughout the estrus cycle. This model has been developed to serve as an animal model of premenstrual irritability. The former group was found to display higher tidal volume variability in diestrus, as compared to the non-aggressive rats. There was no effect of estrus cycle phase on respiratory variability. These results are well in line with the clinical observation that women with premenstrual dysphoria display higher respiratory variability than controls, and the notion that respiratory variability is a parameter of interest in this context. In our opinion, they also strengthen the concept of this animal model as a model of premenstrual irritability.

Serotonin depletion increases respiratory variability in freely moving rats: implications for panic disorder.

To elucidate if serotonergic transmission affects respiratory variability, a parameter consistently found increased in patients with panic disorder, we studied the effect of a serotonin synthesis inhibitor, para-chlorophenylalanine (PCPA), on respiratory variability at baseline and during CO2-induced hyperventilation in awake and unrestrained rats. Forty male Wistar rats were given intraperitoneal injections of PCPA (300 mg/kg) or saline 72, 48 and 24 h before registration of respiration in a plethysmograph allowing the animals to move freely. PCPA-treated rats displayed significantly higher tidal volume variability and minute volume variability, both at baseline and during CO2 exposure, compared to controls. The results support the notion that serotonin dysfunction may contribute to the enhanced respiratory variability observed in patients with panic disorder.

Association between estrus cycle-related changes in respiration and estrus cycle-related aggression in outbred female Wistar rats.

Premenstrual dysphoric disorder is characterized by irritability surfacing during the luteal phase of the menstrual cycle, and disappearing shortly after the onset of menstruation. Although the cardinal symptoms of premenstrual dysphoria are different from those of panic disorder, the two conditions share a number of traits indicating that they both may be associated with abnormalities in the regulation of respiration. Both subjects with panic disorder and subjects with premenstrual dysphoria are hence reported to display enhanced respiratory variability, and to experience anxiety when exposed to CO(2). In the present study, the possible influence of the estrus cycle on respiratory parameters in outbred female rats of the Wistar strain was investigated. Before being tested with respect to respiration, the rats were subdivided into two groups: those displaying estrus cycle-related variation in aggression, as evaluated using the resident intruder paradigm, and those not showing aggression throughout the cycle. Whereas the former group was found to display higher respiratory rate during the diestrus phase than during the proestrus/estrus phase, no cycle-related variation in respiration was observed in animals not showing cycle-related variation in aggression. The results support previous studies indicating that the estrus cycle exerts an influence on respiration, and suggest that rats prone to cycle-related aggression are more sensitive also to the influence of hormonal cyclicity on respiration. The possible bearing of these findings for the aberration in respiration displayed by subjects with premenstrual dysphoria is discussed.