Fig. 8.

Withdrawal from chronic fentanyl exposure affected minute ventilation overshoot response to acute heroin and fentanyl in males but not females. After 4 to 5 days of withdrawal/abstinence from continuous exposure to saline (n = 10 females, 12 males) or fentanyl (n = 10 females, 10 males), rats received an i.v. injection of heroin (600 µg/kg; n = 9 females, 11 males) or fentanyl (25 µg/kg; n = 11 females, 10 males) during two tests 24 hour apart. Heroin induced similar respiratory depression across both sex and treatment, but males in withdrawal from chronic fentanyl had significantly higher overshoot effects than saline-treated males and chronic fentanyl-treated females (A). Maximal decrease in minute ventilation was similar (∼65%) across chronic drug treatment and sex (B). Male rats have significantly higher overshoot effects from fentanyl administration compared with females following a brief respiratory depression, with no differences among treatment groups (C). Maximal decrease in peak inspiratory flow following fentanyl administration was similar (∼70%) across chronic drug treatment and sex (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 as the lowest value within 25 minutes postadministration (B and D). Dashed line indicates average baseline measure, *P < 0.05, male versus female. ^$P < 0.05, male chronic fentanyl versus saline. ^@P < 0.05, male chronic fentanyl versus female chronic fentanyl.