Conditioned Effects of Heroin on Proinflammatory Mediators

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  • March 20, 2019
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  • Szczytkowski, Jennifer Lynn
    • Affiliation: School of Medicine, UNC Neuroscience Center, Neuroscience Curriculum
Abstract
  • Heroin administration alters the induction of nitric oxide, a molecule known to play a critical role in immune function, as well as the production of several proinflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and interleukin-one beta (IL-1β). Previous research has shown that these alterations can be conditioned to environmental stimuli that have been associated with drug administration. The investigations presented here deal with the neural mechanisms whereby these drug cues alter the expression and production of certain proinflammatory mediators essential for host defense. The experiments in Chapter 2 demonstrate that the conditioned alterations in proinflammatory mediators induced by exposure to previously heroin-paired stimuli are a true form of associative learning as they are susceptible to both extinction and latent inhibition. Chapter 3 reveals that the basolateral amygdala (BLA), an area of the brain which has been implicated in the formation of stimulus-reward associations within models of drug abuse, is necessary for the expression of the conditioned response. Administration of a combination of the GABA agonists, muscimol and baclofen, directly into the BLA blocked the conditioned suppression of proinflammatory mediators while administration of these same drugs into an adjacent region of the caudate did not alter the response. The experiments outlined in Chapter 4 show that the pharmacological blockade dopamine, D1 receptors in the BLA reverses the conditioned suppression induced by exposure to previously heroin-paired stimuli. The administration of the dopamine D1 antagonist, SCH23390, but not the D2 antagonist, raclopride, resulted in attenuation of the conditioned effect. These studies are important because they are the first to investigate the neural circuitry involved in the conditioned immune alterations produced by exposure to drug cues. Overall, these findings indicate a need to consider the implications of exposure to drug cues on the immune functioning of current and recovering heroin use.
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  • In Copyright
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  • Lysle, Donald
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  • October 11, 2010

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