Gutierrez Arnold, Taffe Michael A
Department of Psychiatry, University of California, San Diego; La Jolla, CA, USA.
bioRxiv. 2024 May 10:2024.05.06.592492. doi: 10.1101/2024.05.06.592492.
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.
青少年接触毒品与物质滥用和焦虑症相关的更严重心理健康后果有关。本研究的目的是对比青少年期反复吸入海洛因蒸气与成年期类似海洛因接触的长期影响。将雌性Wistar大鼠分组，分别在出生后第36 - 45天或第85 - 94天，每天两次，每次30分钟吸入海洛因或丙二醇（对照）蒸气。对青少年接触组和成年接触组，在吸入蒸气后及四十天后评估痛觉感受。用高架十字迷宫（EPM）评估焦虑样行为，用巴恩斯迷宫评估空间学习能力。分别在出生后第140/189天和第149/198天测定纳洛酮（0.3 mg/kg，腹腔注射）和海洛因（0.5和1.0 mg/kg，皮下注射）对热痛觉感受的急性影响。反复吸入海洛因蒸气在青少年和成年大鼠中均产生跨时段的抗痛觉耐受，青少年表现出更完全的耐受。无论接触年龄如何，吸入海洛因蒸气均产生抗焦虑作用。海洛因对空间学习无影响。除青少年接触海洛因组外，纳洛酮在所有组中均产生急性痛觉过敏，在最高海洛因剂量下，两个海洛因接触组的海洛因抗痛觉作用均减弱。反复吸入海洛因蒸气可对痛觉感受和焦虑样行为产生持续数月的持久影响。重要的是，这些发现表明青少年接触海洛因蒸气会对痛觉感受产生特定影响，而成年期接触则未观察到这种影响。
