Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Granulocyte-colony stimulating factor (G-CSF) enhances cocaine effects in the nucleus accumbens via a dopamine release-based mechanism Cocaine use disorder is associated with alterations in immune function including altered expression of multiple peripheral cytokines in humans - several of which correlate with drug use. Individuals suffering from cocaine use disorder show altered immune system responses to drug-associated cues, highlighting the interaction between the brain and immune system as a critical factor in the development and expression of cocaine use disorder. We have previously demonstrated in animal models that cocaine use upregulates expression of granulocyte colony stimulating factor (G-CSF) - a pleiotropic cytokine - in the serum and the nucleus accumbens (NAc). G-CSF signaling has been causally linked to behavioral responses to cocaine across multiple behavioral domains. The goal of this study was to define whether increases in G-CSF alter the pharmacodynamic effects of cocaine on the dopamine system and whether this occurs via direct mechanisms within local NAc microcircuits. We find that systemic G-CSF injection increases cocaine effects on dopamine terminals. The enhanced dopamine levels in the presence of cocaine occur through a release-based mechanism, rather than through effects on the dopamine transporter - as uptake rates were unchanged following G-CSF treatment. Critically, this effect could be recapitulated by acute bath application of G-CSF to dopamine terminals, an effect that was occluded by prior G-CSF treatment, suggesting a similar mechanistic basis for direct and systemic exposures. This work highlights the critical interaction between the immune system and psychostimulant effects that can alter drug responses and may play a role in vulnerability to cocaine use disorder.
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The categories of this paper are: biophysics
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The categories of this paper are: animal
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The categories of this paper are: immunology
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The categories of this paper are: cell
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The categories of this paper are: behavior
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The categories of this paper are: and
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The categories of this paper are: genomics
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The categories of this paper are: toxicology
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The categories of this paper are: synthetic
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The categories of this paper are: developmental
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The categories of this paper are: biology
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The categories of this paper are: epidemiology
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The categories of this paper are: cognition
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The categories of this paper are: physiology
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The categories of this paper are: cancer
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The categories of this paper are: evolutionary