Persistent effects of repeated adolescent and adult heroin vapor inhalation in female Wistar rats

Adolescent drug exposure has been associated with more severe mental health outcomes related to substance abuse and anxiety disorders. The aim of the present study was to contrast the long-term effects of repeated heroin vapor inhalation during adolescence with similar heroin exposure in adulthood. Groups of female Wistar rats underwent twice daily 30-minute sessions of heroin or propylene glycol (control) vapor inhalation from postnatal days (PND) 36-45 or PND 85-94, respectively. Nociception was assessed after vapor inhalation sessions and forty days later, for the Adolescent-Exposed and Adult-Exposed groups. Anxiety-like behavior was assessed with an elevated plus-maze (EPM) and spatial learning was assessed with a Barnes maze. Acute effects of naloxone (0.3 mg/kg, i.p.) and heroin (0.5 and 1.0 mg/kg, s.c.) on thermal nociception were determined on PND 140/189 and PND 149/198, respectively. Repeated heroin vapor inhalation produced anti-nociceptive tolerance across sessions in both adolescent and adult rats, with the adolescents exhibiting more complete tolerance. Heroin vapor inhalation produced anxiolytic effects, regardless of age of exposure. There were no effects of heroin on spatial learning. Naloxone produced acute hyperalgesia in all but the Adolescent-Exposed heroin group, and heroin anti-nociception was blunted in both heroin-exposed groups at the highest heroin dose. Repeated heroin vapor inhalation can produce lasting effects on nociception and anxiety-like behavior that persist for months after the exposure. Importantly, these findings suggest that adolescent exposure to heroin vapor produces specific effects on nociception that are not observed when exposure occurs in adulthood.