Research and Mental Health Services, VA Boston Healthcare System, Boston, Massachusetts, USA.
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.
Sci Rep. 2023 Aug 25;13(1):13946. doi: 10.1038/s41598-023-40971-3.
Oxycodone is one of the most widely prescribed and misused opioid painkillers in the United States. Evidence suggests that biological sex and hormonal status can impact drug reward in humans and rodents, but the extent to which these factors can influence the rewarding effects of oxycodone is unclear. The purpose of this study was to utilize place conditioning to determine the effects of sex and female hormonal status on the expression of oxycodone conditioned reward in rats. Gonadally intact adult Sprague-Dawley male and female rats were used to test: (1) whether both sexes express conditioned reward to oxycodone at similar doses, (2) the impact of conditioning session length on oxycodone conditioned reward expression in both sexes, and (3) the influence of female estrous cycle stage on oxycodone conditioned reward expression. Both sexes expressed conditioned reward at the same doses of oxycodone. Increasing the length of conditioning sessions did not reveal an effect of sex and resulted in lower magnitude conditioned reward expression. Importantly however, female stage of estrous cycle significantly influenced oxycodone conditioned reward expression. These results suggest that female hormonal status can impact the rewarding effects of opioids and thus have important implications for prescription opioid treatment practices.
羟考酮是美国应用最广泛和滥用最多的阿片类止痛药之一。有证据表明，生物性别和激素状态可以影响人类和啮齿动物的药物奖赏，但这些因素在多大程度上可以影响羟考酮的奖赏效应尚不清楚。本研究旨在利用位置条件作用来确定性别和女性激素状态对大鼠羟考酮条件性奖赏表达的影响。使用成年性成熟的 Sprague-Dawley 雄性和雌性大鼠进行测试：(1) 两性是否以相似的剂量表达对羟考酮的条件性奖赏，(2) Conditioning 会话长度对两性羟考酮条件性奖赏表达的影响，以及 (3) 雌性动情周期阶段对羟考酮条件性奖赏表达的影响。两性在相同剂量的羟考酮下都表现出条件性奖赏。增加 Conditioning 会话的长度并没有显示出性别的影响，并且导致条件性奖赏表达的幅度降低。然而，重要的是，雌性动情周期阶段显著影响羟考酮的条件性奖赏表达。这些结果表明，女性激素状态会影响阿片类药物的奖赏效应，因此对处方阿片类药物治疗实践具有重要意义。
