Alonso I Pamela, O'Connor Bethan M, Bryant Kathleen G, Mandalaywala Rushi K, España Rodrigo A
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, United States.
Addict Neurosci. 2022 Sep;3. doi: 10.1016/j.addicn.2022.100029. Epub 2022 Jul 14.
Relapse to drug use is one of the major challenges in treating substance use disorders. Exposure to drug-related cues and contexts triggers drug craving, which drives cocaine seeking, and increases the probability of relapse. Clinical and animal studies have shown a progressive intensification of cocaine seeking and craving that develops over the course of abstinence, a phenomenon commonly referred to as incubation of cocaine craving. Although the neurobiology underlying incubation of cocaine craving has been examined - particularly within the context of glutamate plasticity- the extent to which increased cocaine craving engenders mesolimbic dopamine (DA) changes has received relatively little attention. To assess whether incubation of cocaine craving is associated with alterations in DA terminal neurotransmission in the nucleus accumbens core (NAc), we used ex vivo fast scan cyclic voltammetry in female and male rats to assess DA dynamics following short access, long access, or intermittent access to cocaine self-administration followed by 28 days of abstinence. Results indicated that both long access and intermittent access to cocaine produced robust incubation of cocaine craving, which was associated with increases in cocaine potency. In addition, intermittent access self-administration also produced a robust increase in DA uptake rate at baseline. In contrast, short access to cocaine did not engender incubation of cocaine craving, nor produce changes in DA neurotransmission. Together these observations indicate that incubation of cocaine craving coincides with changes in DA transmission, suggesting that underlying changes in mesolimbic DA signaling may contribute to the progressive intensification of drug craving that occurs across periods of abstinence.
药物复吸是治疗物质使用障碍的主要挑战之一。接触与药物相关的线索和环境会引发药物渴望，这种渴望驱使人们寻求可卡因，并增加复吸的可能性。临床和动物研究表明，在戒断过程中，寻求可卡因和渴望的行为会逐渐加剧，这一现象通常被称为可卡因渴望的潜伏期。尽管已经对可卡因渴望潜伏期的神经生物学进行了研究——特别是在谷氨酸可塑性的背景下——但可卡因渴望增加在多大程度上导致中脑边缘多巴胺（DA）变化却相对受到较少关注。为了评估可卡因渴望的潜伏期是否与伏隔核核心（NAc）中DA终末神经传递的改变有关，我们对雌性和雄性大鼠进行了离体快速扫描循环伏安法，以评估在短期接触、长期接触或间歇性接触可卡因自我给药并随后戒断28天后的DA动态变化。结果表明，长期接触和间歇性接触可卡因都会产生强烈的可卡因渴望潜伏期，这与可卡因效力的增加有关。此外，间歇性接触自我给药还使基线时的DA摄取率大幅增加。相比之下，短期接触可卡因既不会导致可卡因渴望的潜伏期，也不会引起DA神经传递的变化。这些观察结果共同表明，可卡因渴望的潜伏期与DA传递的变化同时出现，这表明中脑边缘DA信号的潜在变化可能导致戒断期间药物渴望的逐渐加剧。
