Comparison of fentanyl-induced brain oxygen responses following intravenous and intraperitoneal injections in rats

IF 4.6 2区 医学 Q1 NEUROSCIENCES Neuropharmacology Pub Date : 2025-03-12 DOI:10.1016/j.neuropharm.2025.110412
Feonil G. Limiac, Michael R. Noya, Eugene A. Kiyatkin
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Abstract

This study used oxygen sensors coupled with amperometry to examine changes in brain (nucleus accumbens) and peripheral (subcutaneous space) oxygen levels following intravenous (IV) and intraperitoneal (IP) fentanyl injections at different doses. To avoid stress associated with traditional IP injection, fentanyl was delivered via chronically implanted IP catheter. SC oxygen levels decreased in a dose-dependent monophasic manner, whereas brain oxygen responses were more complex, showing modest increases at low fentanyl doses (<3 μg/kg for IV and <10 μg/kg for IP) and biphasic effects (decrease followed by increase) at higher doses (≥10 μg/kg for IV and ≥270 μg/kg for IP). IV-delivered fentanyl elicited faster and stronger responses, with over 10-fold greater potency to induce brain hypoxia compared to IP-fentanyl. Although oxygen response patterns were similar between catheter-based and traditional needle IP injection, the latter caused an ultra-fast brain oxygen increase coupled with rapid oxygen decrease in SC space, suggesting stress as a contributing factor. Interestingly, low-dose, stress-free IP fentanyl administration also induced phasic brain oxygen increases coupled with robust but transient behavioral activation, the effect appears to be independent of drug action on opioid receptors. This effect was attributed to the acidity of fentanyl citrate solution (pH 4.8) and direct actions of H+ on receptive sites on afferents of sensory nerves innervating the abdominal cavity. These findings reveal distinct fentanyl-induced oxygen dynamics based on administration route and highlight the influence of injection stress and drug formulation on oxygen and behavioral responses.

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来源期刊
Neuropharmacology
Neuropharmacology 医学-神经科学
CiteScore
10.00
自引率
4.30%
发文量
288
审稿时长
45 days
期刊介绍: Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).
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