The long-term effects of repeated heroin vapor inhalation during adolescence on measures of nociception and anxiety-like behavior in adult Wistar rats

Abstract

The United States continues to experience a public health crisis related to the nonmedical use of opioid drugs. Adolescents represent a vulnerable group due to increased experimentation with illicit substances that is often associated with the adolescent period, and because adolescent drug use can result in long-term effects that differ from those caused by drug use initiated during adulthood. The present study examined the effects of repeated heroin inhalation, a common route of administering opioids, during adolescence, on measures of nociception and anxiety-like behavior in adulthood. Rats were exposed twice daily to 30-minutes of heroin vapor from post-natal day (PND) 36 to PND 45. At 12 weeks of age, baseline thermal nociception was assessed across a range of temperatures with a warm-water tail-withdrawal assay. Anxiety-like behavior was assessed in an elevated plus-maze (EPM) and activity was measured in an open field arena. Starting at 23 weeks of age, baseline thermal nociception was re-assessed, nociception was determined after acute heroin or naloxone injection, and anxiety-like behavior was redetermined in the EPM. Adolescent heroin inhalation altered baseline thermal nociception in female rats at 12 weeks of age and in both female and male rats at ~23 weeks. Heroin-treated animals exhibited an increase in anxiety-like behavior when tested in the elevated plus-maze, showed blunted heroin-induced analgesia, but exhibited no effect on naloxone-induced hyperalgesia. The present study demonstrates for the first time that heroin vapor inhalation during adolescence produces behavioral and physiological consequences in rats that persist well into adulthood.