دورية أكاديمية

Inflammatory Pain Promotes Increased Opioid Self-Administration: Role of Dysregulated Ventral Tegmental Area μ Opioid Receptors.

التفاصيل البيبلوغرافية
العنوان: Inflammatory Pain Promotes Increased Opioid Self-Administration: Role of Dysregulated Ventral Tegmental Area μ Opioid Receptors.
المؤلفون: Hipólito, Lucia, Wilson-Poe, Adrianne, Campos-Jurado, Yolanda, Elaine Zhong, Gonzalez-Romero, Jose, Virag, Laszlo, Whittington, Robert, Comer, Sandra D., Carlton, Susan M., Walker, Brendan M., Bruchas, Michael R., Morón, Jose A.
المصدر: Journal of Neuroscience; 9/2/2015, Vol. 35 Issue 35, p12217-12231, 15p
مصطلحات موضوعية: PAIN management, DRUG administration, OPIOID receptors, HEROIN, DOPAMINE, MICRODIALYSIS, PHENOTYPES
مستخلص: Pain management in opioid abusers engenders ethical and practical difficulties for clinicians, often resulting in pain mismanagement. Although chronic opioid administration may alter pain states, the presence of pain itself may alter the propensity to self-administer opioids, and previous history of drug abuse comorbid with chronic pain promotes higher rates of opioid misuse. Here, we tested the hypothesis that inflammatory pain leads to increased heroin self-administration resulting from altered mu opioid receptor (MOR) regulation of mesolimbic dopamine (DA) transmission. To this end, the complete Freund's adjuvant (CFA) model of inflammation was used to assess the neurochemical and functional changes induced by inflammatory pain on MOR-mediated mesolimbicDAtransmission and on rat intravenous heroin self-administration under fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. In the presence of inflammatory pain, heroin intake under an FR schedule was increased for high, but attenuated for low, heroin doses with concomitant alterations in mesolimbicMORfunction suggested byDAmicrodialysis. Consistent with the reduction in low doseFRheroin self-administration, inflammatory pain reduced motivation for a low dose of heroin, as measured by responding under a PR schedule of reinforcement, an effect dissociable from high heroin dose PR responding. Together, these results identify a connection between inflammatory pain and loss of MOR function in the mesolimbic dopaminergic pathway that increases intake of high doses of heroin. These findings suggest that pain-induced loss ofMORfunction in the mesolimbic pathway may promote opioid dose escalation and contribute to opioid abuse-associated phenotypes. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:02706474
DOI:10.1523/JNEUROSCI.1053-15.2015