Granulocyte colony-stimulating factor (G-CSF) enhances cocaine effects in the nucleus accumbens via a dopamine release –based mechanism

AbstractCocaine 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 the 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 mu ltiple 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 ap plication of G-CSF to dopamine terminals, an effect that was occluded by prior G-CSF treatment, suggesting a similar mechanistic basis for direct a...

Source: Psychopharmacology - September 6, 2021 Category: Psychiatry Source Type: research