Department of Psychology, California State University San Marcos, 333 S. Twin Oaks Valley Rd, San Marcos, CA 92096, USA.
Pharmacol Biochem Behav. 2023 Jun;227-228:173581. doi: 10.1016/j.pbb.2023.173581. Epub 2023 Jun 7.
Initiation of non-medical dextromethorphan (DXM) use often occurs in adolescence, yet little is known about the consequences when use begins during this developmental period. The current experiments examined the acute response and the effects of repeated exposure to DXM in adolescence on behavior in adulthood. We examined locomotor activity, locomotor sensitization, and cognitive function, in rats that received repeated administration of DXM. Groups of adolescent (PND 30) and adult (PND 60) male rats were treated with DXM (60 mg/kg) once daily for 10 days. Locomotor activity in response to DXM was assessed following the first injection, on the 10th day of injection (adolescent - PND 39; adult - PND 69), and following 20 days of abstinence (adolescent - PND 59; adult - PND 89). Acute locomotor effects and locomotor sensitization were compared in adolescents and adults; cross-sensitization to ketamine, another dissociative with abuse potential, was also examined. In a separate group of rodents cognitive deficits were assessed following a 20 day abstinence period (adolescent - PND 59; adult - PND 89) in spatial learning and novel object recognition tasks. The locomotor stimulant effect of DXM was much greater in adolescents than adults. Also, only adolescent rats that were repeatedly administered DXM demonstrated locomotor sensitization at the end of 10 days of injection. However, sensitization occurred after the abstinence period in all rats regardless of age. Nonetheless, cross-sensitization to ketamine was only evident in adolescent-treated rats. DXM also led to an increase in perseverative errors in reversal learning only in the adolescent-treated group. We conclude that repeated use of DXM produces long-lasting neuroadaptations that may contribute to addiction. Deficits in cognitive flexibility occur in adolescents, although further work is necessary to confirm these findings. The results extend the understanding of potential long-term consequences of DXM use in adolescents and adults.
非医疗用右美沙芬（DXM）的使用通常始于青少年时期，但对于在这一发育阶段开始使用时会产生哪些后果，人们知之甚少。目前的实验研究了在青少年时期重复使用 DXM 对成年期行为的急性反应和影响。我们检查了接受重复 DXM 给药的大鼠的运动活动、运动敏化和认知功能。一组青少年（PND 30）和成年（PND 60）雄性大鼠每天接受 DXM（60mg/kg）一次治疗，共 10 天。在第一次注射后、第 10 天注射时（青少年-PND 39；成年-PND 69）以及 20 天戒断后（青少年-PND 59；成年-PND 89）评估了对 DXM 的运动反应。比较了青少年和成年人的急性运动效应和运动敏化；还检查了另一种具有滥用潜力的分离剂氯胺酮的交叉敏化。在另一组啮齿动物中，在 20 天戒断期后（青少年-PND 59；成年-PND 89）评估了空间学习和新物体识别任务中的认知缺陷。与成年人相比，DXM 的运动兴奋剂作用在青少年中要强得多。此外，只有在反复接受 DXM 治疗的青少年大鼠中，在 10 天注射结束时才表现出运动敏化。然而，无论年龄大小，所有大鼠在戒断期后都出现了敏化。然而，只有在接受 DXM 治疗的青少年大鼠中才出现对氯胺酮的交叉敏化。DXM 还仅在接受 DXM 治疗的青少年组中导致反转学习中持续错误增加。我们得出结论，重复使用 DXM 会产生持久的神经适应，可能导致成瘾。认知灵活性缺陷发生在青少年中，尽管需要进一步的工作来证实这些发现。这些结果扩展了对青少年和成年人使用 DXM 的潜在长期后果的理解。
