Hypercapnic ventilatory response of anesthetized female rats subjected to neonatal maternal separation: insight into the origins of panic attacks?

Neonatal maternal separation (NMS) is a form of stress that interferes with the regulation of the stress response, an effect that predisposes to the emergence of panic and anxiety related disorders. We previously showed that at adulthood, awake female (but not male) rats subjected to NMS show a hypercapnic ventilatory response (HCVR; 5% CO2) that is 63% greater than controls (Genest et al., 2007). To understand the mechanisms underlying the sex-specific effects of NMS on the ventilatory response to CO2, we used two different anesthetized female rat preparations to assess central CO2 chemosensitivity and contribution of sensory afferents (stretch receptors and peripheral chemoreceptors) that influence the HCVR. Data show that anesthesia eliminated the respiratory phenotype observed previously in awake females and CO2 chemosensitivity did not differ between groups. Finally, the assessment of the ovarian hormone levels across the oestrus cycle failed to reveal significant differences between groups. Since anesthesia did not affect the manifestation of NMS-related respiratory dysfunction in males (including the hypercapnic ventilatory response) (Kinkead et al., 2005; Dumont and Kinkead, 2010), we propose that the panic or anxiety induced by CO2 during wakefulness is responsible for enhancement of the HCVR in NMS females.