Enhancement of CO₂-Induced Anxiety in Healthy Volunteers With the Serotonin Antagonist Metergoline

OBJECTIVE: The mechanism of action of CO₂-induced anxiety is unknown and has been little studied. The authors studied healthy volunteers for the possible influence of serotonin (5-HT) on CO₂-induced anxiety. METHOD: Fourteen healthy volunteers received two vital capacity inhalations each of 35% CO₂ and of air, preceded once by placebo and once by the 5-HT antagonist metergoline in a double-blind, randomized crossover design. RESULTS: Mean National Institute of Mental Health self-rating anxiety subscale scores increased ­nonsignificantly after CO₂ inhalation; this effect was significantly enhanced by the administration of metergoline. CONCLUSIONS: The authors hypothesize that 5-HT may inhibit ­­CO₂-induced anxiety, a function that is lessened by metergoline.