title: Controlled cross-over study in normal subjects of naloxone-preceding-lactate infusions; respiratory and subjective responses: relationship to endogenous opioid system, suffocation false alarm theory and childhood parental loss.
abstract: BACKGROUND
  The expanded suffocation false alarm theory (SFA) hypothesizes that dysfunction in endogenous opioidergic regulation increases sensitivity to CO2, separation distress and panic attacks. In panic disorder (PD) patients, both spontaneous clinical panics and lactate-induced panics markedly increase tidal volume (TV), whereas normals have a lesser effect, possibly due to their intact endogenous opioid system. We hypothesized that impairing the opioidergic system by naloxone could make normal controls parallel PD patients' response when lactate challenged. Whether actual separations and losses during childhood (childhood parental loss, CPL) affected naloxone-induced respiratory contrasts was explored. Subjective panic-like symptoms were analyzed although pilot work indicated that the subjective aspect of anxious panic was not well modeled by this specific protocol.
  
  
  METHODS
  Randomized cross-over sequences of intravenous naloxone (2 mg/kg) followed by lactate (10 mg/kg), or saline followed by lactate, were given to 25 volunteers. Respiratory physiology was objectively recorded by the LifeShirt. Subjective symptomatology was also recorded.
  
  
  RESULTS
  Impairment of the endogenous opioid system by naloxone accentuates TV and symptomatic response to lactate. This interaction is substantially lessened by CPL.
  
  
  CONCLUSIONS
  Opioidergic dysregulation may underlie respiratory pathophysiology and suffocation sensitivity in PD. Comparing specific anti-panic medications with ineffective anti-panic agents (e.g. propranolol) can test the specificity of the naloxone+lactate model. A screen for putative anti-panic agents and a new pharmacotherapeutic approach are suggested. Heuristically, the experimental unveiling of the endogenous opioid system impairing effects of CPL and separation in normal adults opens a new experimental, investigatory area.
authors.affiliation: Department of Psychiatry, Columbia University, and New York State Psychiatric Institute, New York, NY, USA. mpreter@gmail.com
authors.forename: M
authors.initials: M
authors.lastname: Preter
authors.forename: S H
authors.initials: SH
authors.lastname: Lee
authors.forename: E
authors.initials: E
authors.lastname: Petkova
authors.forename: M
authors.initials: M
authors.lastname: Vannucci
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: D F
authors.initials: DF
authors.lastname: Klein
mesh_terms: D000293:Adolescent; D000328:Adult; D001010:Anxiety, Separation / Q000378:metabolism*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D019344:Lactic Acid; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology; D018847:Opioid Peptides / Q000187:drug effects / Q000378:metabolism*; D016584:Panic Disorder / Q000378:metabolism*; D012143:Respiratory Physiological Phenomena / Q000187:drug effects
chemical_list: D018847:Opioid Peptides; D019344:Lactic Acid; D009270:Naloxone
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