Differential behavioral sensitivity to carbon dioxide (CO2) inhalation in rats. (27th March 2017)

• Record Type: Journal Article
• Authors: Winter, Andrew; Ahlbrand, Rebecca; Naik, Devanshi; Sah, Renu
• Is Part Of: Neuroscience. Volume 346(2017)
• Page Start: 423
• Page End: 433
• Publication Date: 2017-03-27
• Subjects: BSA bovine serum albumin -- DR dorsal raphe -- DRD dorsal region -- DRVL dorsal raphe ventrolateral -- DβH dopamine β hydroxylase -- LC locus coeruleus -- NA noradrenaline -- PD panic disorder -- SD Sprague–Dawley -- TPH tryptophan hydroxylase -- TPH-2 tryptophan hydroxylase 2 -- VLPAG ventrolateral periaqueductal grey; panic -- CO2 sensitivity -- serotonergic -- noradrenergic -- dorsal raphe -- locus coeruleus; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2017.01.003
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: CO2 inhalation, a biological challenge for panic and fear elicits differential behavioral sensitivity in rat strains. Long Evans and Wistar-Kyoto rats show significantly higher CO2 -evoked immobility than Wistar and Sprague–Dawley rats. CO2 -sensitive strains have decreased TPH2-positive serotonergic neurons in panic regulatory raphe subnuclei, DRVL-VLPAG. CO2 -sensitive strains have increased DβH-positive noradrenergic neurons in the locus coeruleus, a CO2 -chemosensitive site. Rodent models of CO2 -sensitivity will facilitate understanding of CO2 -hypersensitivity in panic and anxiety disorders. Abstract: Inhalation of carbon dioxide (CO2 ) is frequently employed as a biological challenge to evoke intense fear and anxiety. In individuals with panic disorder, CO2 reliably evokes panic attacks. Sensitivity to CO2 is highly heterogeneous among individuals, and although a genetic component is implicated, underlying mechanisms are not clear. Preclinical models that can simulate differential responsivity to CO2 are therefore relevant. In the current study we investigated CO2 -evoked behavioral responses in four different rat strains: Sprague–Dawley (SD), Wistar (W), Long Evans (LE) and Wistar-Kyoto, (WK) rats. We also assessed tryptophan hydroxylase 2 (TPH-2)-positive serotonergic neurons in anxiety/panic regulatory subdivisions of the dorsal raphe nucleus (DR), as well as dopamine β hydroxylase (DβH)-positive noradrenergic neurons in the locus coeruleus, implicated in central CO2 -chemosensitivity. Behavioral responsivity to CO2 inhalation varied between strains. CO2 -evoked immobility was significantly higher in LE and WK rats as compared with W and SD cohorts. Differences were also observed in CO2 -evoked rearing and grooming behaviors. Exposure to CO2 did not produce conditioned behavioral responses upon re-exposure to CO2 context in any strain. Reduced TPH-2-positive cell counts were observed specifically in the panic-regulatory dorsal raphe ventrolateral (DRVL)-ventrolateral periaqueductal gray (VLPAG) subdivision in CO2 -sensitive strains. Conversely, DβH-positive cell counts within the LC were significantly higher in CO2 -sensitive strains. Collectively, our data provide evidence for strain dependent, differential CO2 -sensitivity and potential differences in monoaminergic systems regulating panic and anxiety. Comparative studies between CO2 -vulnerable and resistant strains may facilitate the mechanistic understanding of differential CO2 -sensitivity in the development of panic and anxiety disorders.