Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Instituto de Investigación Biomédica de Málaga (IBIMA), Facultad de Psicología, Universidad de Málaga, Campus de Teatinos S/N, Málaga 29071, Spain.
Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Avenida Carlos Haya 82, 29010 Málaga, Spain.
Pharmacol Biochem Behav. 2018 Mar;166:1-12. doi: 10.1016/j.pbb.2018.01.002. Epub 2018 Jan 11.
Cocaine addiction is a chronically relapsing disorder characterized by compulsive drug-seeking and drug-taking behaviors. Previous studies have demonstrated that cocaine, as well as other drugs of abuse, alters the levels of lipid-based signaling molecules, such as N-acylethanolamines (NAEs). Moreover, brain levels of NAEs have shown sensitivity to cocaine self-administration and extinction training in rodents. Given this background, the aim of this study was to investigate the effects of repeated or acute administration of palmitoylethanolamide (PEA), an endogenous NAE, on psychomotor sensitization and cocaine-induced contextual conditioning. To this end, the potential ability of repeated PEA administration (1 or 10 mg/kg, i.p.) to modulate the acquisition of cocaine-induced behavioral sensitization (BS) and conditioned place preference (CPP) was assessed in male C57BL/6J mice. In addition, the expression of cocaine-induced BS and CPP following acute PEA administration were also studied. Results showed that repeated administration of both doses of PEA were able to block the acquisition of cocaine-induced BS. Furthermore, acute administration of both doses of PEA was able to abolish the expression of BS, while the highest dose also abolished the expression of cocaine-induced CPP. Taken together, these results indicate that exogenous administration of PEA attenuated psychomotor sensitization, while the effect of PEA in cocaine-induced CPP depended on whether PEA was administered repeatedly or acutely. These findings could be relevant to understand the role that NAEs play in processes underlying the development and maintenance of cocaine addiction.
可卡因成瘾是一种慢性复发性疾病，其特征是强迫性觅药和用药行为。先前的研究表明，可卡因和其他滥用药物会改变脂质信号分子的水平，如 N-酰基乙醇胺（NAE）。此外，NAE 的脑水平对啮齿动物的可卡因自我给药和消退训练表现出敏感性。鉴于此，本研究旨在研究重复或急性给予棕榈酰乙醇酰胺（PEA）（一种内源性 NAE）对精神运动敏化和可卡因诱导的条件性位置偏好的影响。为此，评估了重复给予 PEA（1 或 10mg/kg，ip）对雄性 C57BL/6J 小鼠可卡因诱导的行为敏化（BS）和条件性位置偏好（CPP）获得的潜在能力。此外，还研究了急性给予 PEA 后可卡因诱导的 BS 和 CPP 的表达。结果表明，两种剂量的 PEA 重复给药均能阻断可卡因诱导的 BS 的获得。此外，两种剂量的 PEA 急性给药均能消除 BS 的表达，而最高剂量也能消除可卡因诱导的 CPP 的表达。总之，这些结果表明外源性给予 PEA 可减弱精神运动敏化，而 PEA 在可卡因诱导的 CPP 中的作用取决于 PEA 是重复给予还是急性给予。这些发现可能与理解 NAE 在可卡因成瘾发展和维持过程中的作用有关。
