Characterization of serum and brain cytokine levels following prolonged binge-like methamphetamine self-administration and cued methamphetamine seeking

Abstract

Methamphetamine (METH) use is associated with peripheral and brain inflammation that can contribute to METH-associated toxicity and heightened cue reactivity. However, the persistence of these phenomena, especially with regards to changes in brain proinflammatory cytokine levels, is not yet clear. In this study, we determined the effects of repeated binge-like METH self-administration (96-h/week for 3 weeks) followed by cued drug seeking for up to 60 days into abstinence in male and female rats. Serum cytokine levels were assessed prior to cued drug seeking tests on days 21 and 60 of abstinence, and cytokine levels in the prefrontal cortex (PFC) and dorsal striatum (DStr) were assessed on the day following that last cued seeking test. We observed robust levels of METH intake in both sexes as well as a gradual increase in magnitude of METH seeking across abstinence that did not differ between sexes. Magnitude of METH seeking on days 10 and 60 were positively correlated with prior total drug intake. Sex- and region-dependent changes in various chemokines and interleukins were observed in the PFC and DStr, as were sex- and time-dependent changes in serum cytokine levels, with the largest number of cytokines altered on day 60 in male animals. Serum levels of IL-6 were positively correlated with brain levels of this cytokine, but serum levels of this and other cytokines did not correlate with the magnitude of METH seeking. These findings suggest that binge-like METH intake produces persistent yet divergent central and peripheral immune responses that extend well into abstinence.