Fig. 2.

Minute ventilation was robustly decreased across several doses of heroin and fentanyl. Minute ventilation was decreased by a single i.v. dose of heroin (300, 600, or 1200 µg/kg; n = 10 female, 11 male) or fentanyl (12, 25, or 50 µg/kg; n = 10 female, 10 male) compared with vehicle. Each dose of heroin elicited decreases in minute ventilation, with higher doses producing prolonged effects for up to 50 min and no difference between males and females over time (A). Minute ventilation maximally decreased to ∼50% of baseline following heroin administration, which was significantly different from vehicle for all doses; overall, females had significantly lower values than males (B). Fentanyl administration elicited shorter-lasting decreases in minute ventilation, with higher doses producing prolonged effects for up to 15 minutes and no difference between the sexes (C). Maximum decreases following fentanyl administration were independent of sex, with decreases to ∼60% of baseline that were significantly different from vehicle for the middle and high doses (D). Data are expressed as mean ± S.D. in percentage of baseline in 5-minute bins over −20 to 60 minutes postadministration (A and C) or lowest 5-minute bin value within 25 minutes postadministration (B and D). Dashed line indicates average baseline measure. Filled-in symbols indicate significant difference, P < 0.05, from vehicle group, with gray color indicating overshoot/recovery (i.e., not respiratory depression). *P < 0.05; **P < 0.001, compared with vehicle. ♀, female; ♂, male.