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Sex differences in addiction and the innate immune response

Project Full Title:

Sex differences in addiction-like behaviors, macrophage trafficking, and response to drugs of abuse.

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Project Description:

This project is specifically housed within the Hope College Department of Biology. Recent evidence suggests a critical component of drug-induced toxicity and dependence involves the activation of non-neuronal cells in the central nervous system (CNS). For example, several rodent studies have proposed that the CNS immune response to drugs of abuse, e.g. increased pro-inflammatory cytokine production, is due to direct activation of microglia, the resident immune defense cells in the CNS, and may underlie its negative consequences. However, ethanol, morphine, and THC exposure is systemic, and differential regulation of CNS vs. peripheral immune responses after chronic exposures are reported. It currently hypothesized that peripheral immune responses significantly impact the brain and behavior, either directly via leukocyte entry, or indirectly via humoral or neuronal modulation by systemic factors. The major objectives of this study are twofold: 1) to understand the differential origins of microglia (i.e. the resident immune cells of the brain) and peripherally-derived brain macrophages (i.e. from the blood, liver, spleen, etc.,) after drugs of abuse (ethanol, morphine, and tetrahydrocannabinol [THC]) in males and females; and 2) to determine the role of peripherally-derived brain macrophages in addiction-like behaviors.

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