title: Interaction between δ opioid receptors and benzodiazepines in CO₂-induced respiratory responses in mice.
abstract: The false-suffocation hypothesis of panic disorder (Klein, 1993) suggested δ-opioid receptors as a possible source of the respiratory dysfunction manifested in panic attacks occurring in panic disorder (Preter and Klein, 2008). This study sought to determine if a lack of δ-opioid receptors in a mouse model affects respiratory response to elevated CO₂, and whether the response is modulated by benzodiazepines, which are widely used to treat panic disorder. In a whole-body plethysmograph, respiratory responses to 5% CO₂ were compared between δ-opioid receptor knockout mice and wild-type mice after saline, diazepam (1mg/kg), and alprazolam (0.3mg/kg) injections. The results show that lack of δ-opioid receptors does not affect normal response to elevated CO₂, but does prevent benzodiazepines from modulating that response. Thus, in the presence of benzodiazepine agonists, respiratory responses to elevated CO₂ were enhanced in δ-opioid receptor knockout mice compared to wild-type mice. This suggests an interplay between benzodiazepine receptors and δ-opioid receptors in regulating the respiratory effects of elevated CO₂, which might be related to CO₂ induced panic.
authors.affiliation: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
authors.forename: Anne H
authors.initials: AH
authors.lastname: Borkowski
authors.forename: Dylan C
authors.initials: DC
authors.lastname: Barnes
authors.forename: Derek R
authors.initials: DR
authors.lastname: Blanchette
authors.forename: F Xavier
authors.initials: FX
authors.lastname: Castellanos
authors.forename: Donald F
authors.initials: DF
authors.lastname: Klein
authors.forename: Donald A
authors.initials: DA
authors.lastname: Wilson
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002245:Carbon Dioxide / Q000097:blood / Q000633:toxicity*; D004195:Disease Models, Animal; D006935:Hypercapnia / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016584:Panic Disorder / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D010993:Plethysmography, Whole Body / Q000379:methods; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D017465:Receptors, Opioid, delta / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012131:Respiratory Insufficiency / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D013990:Tidal Volume / Q000502:physiology
chemical_list: D011963:Receptors, GABA-A; D017465:Receptors, Opioid, delta; D001569:Benzodiazepines; D002245:Carbon Dioxide