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The effect of the μ-opioid receptor antagonist naloxone on extinction of conditioned fear in the developing rat

机译:μ阿片受体拮抗剂纳洛酮对发育中大鼠条件性恐惧消退的影响

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Several recent studies report that neurotransmitters that are critically involved in extinction in adult rats are not important for extinction in young rats. Specifically, pretest injection of the γ-aminobutryic acid (GABA) receptor inverse agonist FG7142 has no effect on extinction in postnatal day (P)17 rats, although it reverses extinction in P24 rats as reported by Kim and Richardson in an earlier paper. Further, pre-extinction injection of the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 has no effect on extinction in P17 rats, whereas it impairs long-term extinction in P24 rats as per Langton and colleagues in an earlier work. These findings indicate that extinction in P17 rats is qualitatively different from extinction in older rats. The present study examines the involvement of the endogenous opioid system in extinction in the developing rat using systemic injections of the μ-opioid receptor antagonist naloxone. Experiment 1 showed that injection of naloxone before extinction training disrupted the acquisition of extinction in both P17 and P24 rats. This effect was dependent on central rather than peripheral μ-opioid receptors (Experiment 2), and neither pre-test nor post-extinction injection of naloxone had effects on extinction (Experiments 3 and 4). Taken together, these findings indicate that opioid neurotransmission, in contrast to GABA and NMDA activity, is critical for extinction acquisition across development.
机译:最近的几项研究报告说,成年大鼠灭绝中关键参与的神经递质对于年轻大鼠的灭绝并不重要。具体而言,如Kim和Richardson在较早的论文中所报道的那样,预先测试注射γ-氨基丁酸(GABA)受体反向激动剂FG7142对出生后(P)17大鼠的灭绝没有影响,尽管它可以逆转P24大鼠的灭绝。此外,灭绝前注射N-甲基-d-天冬氨酸(NMDA)受体拮抗剂MK-801对P17大鼠绝种没有影响,而根据Langton及其同事在早期的研究,它会损害P24大鼠的长期绝种。工作。这些发现表明,P17大鼠的灭绝与老年大鼠的灭绝在质量上是不同的。本研究使用系统性注射μ阿片受体拮抗剂纳洛酮的方法,检查了发育中大鼠内源性阿片系统的灭绝情况。实验1表明在灭绝训练之前注射纳洛酮会破坏P17和P24大鼠的灭绝获得。该效应取决于中枢而非阿片类阿片受体(实验2),并且纳洛酮试验前或灭绝后注射纳洛酮均对灭绝没有影响(实验3和4)。两者合计,这些发现表明,与GABA和NMDA活性相反,阿片类神经传递对于整个发育过程中的灭绝习性至关重要。

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