成年期和青春期开始的羟考酮自我给药后雄性大鼠对羟考酮渴望的诱导
Incubation of Oxycodone Craving Following Adult-Onset and Adolescent-Onset Oxycodone Self-Administration in Male Rats.
作者信息
Altshuler Rachel D, Garcia Kristine T, Li Xuan
机构信息
Department of Psychology, University of Maryland, College Park, College Park, MD, United States.
出版信息
Front Behav Neurosci. 2021 Jun 23;15:697509. doi: 10.3389/fnbeh.2021.697509. eCollection 2021.
Relapse is a major obstacle to curb the ongoing epidemic of prescription opioid abuse. We and others previously demonstrated that oxycodone seeking in adult rats progressively increases after abstinence from oxycodone self-administration (incubation of oxycodone craving). In humans, the onset of oxycodone use in adolescents may increase individuals' vulnerability to later opioid addiction. However, little is known about incubation of oxycodone craving after adolescent-onset oxycodone self-administration in rats. In the first study, we trained single-housed adolescent (postnatal day 35 at start) and adult (postnatal day 77 at start) male Sprague-Dawley rats to self-administer oxycodone (0.1 mg/kg/infusion, 6 h/day for 10 days) and then tested oxycodone relapse on both abstinence day 1 and day 15. Given that social experience is critical for neurobehavioral development in adolescents, we performed the second study using group-housed adolescent and adult rats. In both studies, we observed no age differences in oxycodone self-administration and incubated oxycodone seeking on abstinence day 15. However, on abstinence day 1, we observed decreased oxycodone seeking in adolescents compared with adults. This pattern of data led to elevated incubation slopes in adolescent rats compared with adult rats. Finally, group-housed rats exhibited attenuated oxycodone seeking compared with single-housed rats on abstinence day 15, but not on day 1. Taken together, these data suggest that adolescents may be resistant to oxycodone relapse during early abstinence, but this resistance dissipates quickly during the transition between adolescent and young adulthood. In addition, group-housing plays a protective role against incubated oxycodone craving.
复发是遏制当前处方阿片类药物滥用流行的主要障碍。我们和其他研究人员先前已证明,成年大鼠在停止阿片类药物自我给药后,对羟考酮的觅药行为会逐渐增加(羟考酮渴求的潜伏期)。在人类中,青少年开始使用羟考酮可能会增加其日后对阿片类药物成瘾的易感性。然而,对于大鼠青春期开始的羟考酮自我给药后羟考酮渴求的潜伏期,人们了解甚少。在第一项研究中,我们训练单笼饲养的青春期雄性Sprague-Dawley大鼠(开始时出生后35天)和成年雄性Sprague-Dawley大鼠(开始时出生后77天)自我给药羟考酮(0.1mg/kg/输注,每天6小时,共10天),然后在戒断第1天和第15天测试羟考酮复发情况。鉴于社交经验对青少年的神经行为发育至关重要,我们在第二项研究中使用了群居的青春期和成年大鼠。在两项研究中,我们均未观察到羟考酮自我给药及戒断第15天羟考酮觅药潜伏期的年龄差异。然而,在戒断第1天,我们观察到与成年大鼠相比,青春期大鼠的羟考酮觅药行为减少。这种数据模式导致青春期大鼠的潜伏期斜率高于成年大鼠。最后,在戒断第15天,群居大鼠与单笼饲养大鼠相比,羟考酮觅药行为减弱,但在第1天未出现这种情况。综上所述,这些数据表明,青少年在早期戒断期间可能对羟考酮复发具有抵抗力,但这种抵抗力在青少年向青年期过渡期间会迅速消失。此外,群居对羟考酮渴求潜伏期具有保护作用。