Szczytkowski Jennifer L, Lysle Donald T
Department of Psychology and Curriculum in Neurobiology, CB#3270, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3270, USA.
Psychopharmacology (Berl). 2007 May;191(4):879-89. doi: 10.1007/s00213-006-0673-z. Epub 2007 Jan 9.
The administration of heroin has been shown to inhibit the induction of nitric oxide, a molecule known to play a critical role in immune function. Previous research has shown that this alteration can be conditioned to environmental stimuli that have been associated with drug administration. However, it remains unknown whether the conditioned effects of heroin on nitric oxide formation follow accepted principles of learning.
This study sought to determine whether manipulations that induce extinction and latent inhibition, two learning paradigms known to reduce the expression of conditioned responses, would alter heroin's conditioned effects on the expression of inducible nitric oxide synthase (iNOS).
The conditioning procedure involved repeated pairing of heroin administration with placement into a standard conditioning chamber. Rats were repeatedly exposed to the chambers without heroin reinforcement to determine whether the conditioned response would extinguish. To induce latent inhibition, rats received repeated exposure to the chamber before the start of conditioning to inhibit the acquisition of the conditioned response. Ten days after the final conditioning session, all rats were injected with lipopolysaccharide (LPS) to induce iNOS expression. Spleen and liver tissue were removed to determine iNOS expression using reverse transcriptase polymerase chain reaction. Blood was collected to determine the concentration of nitrite/nitrate.
The results showed that both extinction and latent inhibition reduced the conditioned effects of heroin on the production of nitric oxide.
This study provides the first evidence that the conditioned effects of heroin on nitric oxide production follow accepted principles of learning.
已证明给予海洛因会抑制一氧化氮的诱导，一氧化氮是一种在免疫功能中起关键作用的分子。先前的研究表明，这种改变可以与药物给药相关的环境刺激形成条件反射。然而，海洛因对一氧化氮形成的条件反射效应是否遵循公认的学习原则仍不清楚。
本研究旨在确定诱导消退和潜伏抑制这两种已知可减少条件反应表达的学习范式的操作是否会改变海洛因对诱导型一氧化氮合酶（iNOS）表达的条件反射效应。
条件反射程序包括将海洛因给药与放入标准条件反射箱反复配对。大鼠反复暴露于无海洛因强化的箱中，以确定条件反应是否会消退。为了诱导潜伏抑制，大鼠在条件反射开始前反复暴露于箱中，以抑制条件反应的习得。在最后一次条件反射训练后10天，所有大鼠注射脂多糖（LPS）以诱导iNOS表达。取出脾脏和肝脏组织，使用逆转录聚合酶链反应确定iNOS表达。采集血液以确定亚硝酸盐/硝酸盐浓度。
结果表明，消退和潜伏抑制均降低了海洛因对一氧化氮产生的条件反射效应。
本研究提供了首个证据，表明海洛因对一氧化氮产生的条件反射效应遵循公认的学习原则。
