The Long‐Term Effects of Repeated Heroin Vapor Inhalation During Adolescence in Adult Wistar Rats

Abstract

Although inhalation is a common route for the administration of illicit opioid drugs, there are only a few animal studies on the effects of inhaled opioids. The present work aimed to assess the behavioral effects of repeated heroin vapor exposure during adolescence on measures of nociception, anxiety, and locomotor activity later in adulthood. To this end, adolescent female and male Wistar rats were exposed to heroin vapor for 30 minutes twice daily for 10 days starting on PND 36. Upon reaching adulthood, warm-water tail-withdrawal tests were performed to assess baseline thermal nociception, and anxiety-like behavior was measured in an elevated-plus maze. Next, locomotor activity was measured in an open field arena. The persistence of nociceptive effects was examined after a period of time, starting 29 weeks of age. This included assessments on baseline thermal nociception across a range of temperatures and warm-water tail-withdrawal tests following injected heroin. We report effects on baseline thermal nociception at 12 weeks of age and an increase in anxiety-like behavior in the elevated-plus maze. Additionally, locomotor behavior was affected by adolescent heroin vapor. When baseline nociception was once again measured at 29 weeks of age, the effects adolescent heroin vapor persisted and the anti-nociceptive effects of injected heroin were blunted in animals previously exposed to heroin vapor. The findings here recapitulate the nociceptive and anxiogenic effects of opioids reported in previous studies using parenteral injection as the route of administration and extend them to inhalation, a common yet understudied route of administering opioid drugs. Importantly, we report a persistence of effects of opioid exposure on nociception that is not well-described in the current literature.