Abstract
Drug-induced immunosuppression may underline increased hypothalamic–pituitary–adrenal axis response to stress observed following chronic psychostimulant treatment. However, the consequences of random amphetamine (AMPH) treatment, withdrawal and AMPH challenge after withdrawal on the peripheral immunity and systemic corticosterone response are unknown. In this study, the total blood and spleen leukocyte, lymphocyte, T, B, NK, TCD4+/TCD8+ cell numbers and ratio, pro-inflammatory interferon gamma (IFN-γ), and anti-inflammatory interleukin-4 (IL-4) production, and plasma corticosterone concentration in Wistar rats were investigated after: chronic, random AMPH/SAL treatment alone (20 injections in 60 days, 1 mg/kg b.w., i.p.), AMPH/SAL withdrawal (for 20 consecutive days after random AMPH/SAL exposure) or AMPH/SAL challenge after withdrawal (single injection after the AMPH/SAL withdrawal phase). The results showed blood and spleen leukopenia, lymphopenia, lower blood production of IFN-ɤ, and increased plasma corticosterone concentration after the AMPH treatment, which were more pronounced in the AMPH after withdrawal group. In contrast, an increased number of blood NK cells and production of IL-4 after chronic, random AMPH treatment alone, were found. Blood AMPH-induced leukopenia and lymphopenia were due to decreased total number of T, B lymphocytes and, at least in part, of granulocytes and monocytes. Moreover, decreases in the number of blood TCD4+ and TCD8+ lymphocytes both in the AMPH chronic alone and withdrawal phases, were found.The major findings of this study are that AMPH treatment after the long-term withdrawal from previous random AMPH exposure, accelerates the drug-induced immunosuppressive and systemic corticosterone responses, suggesting prolonged immunosuppressive effects and an increase in incidence of infectious diseases.Graphical Prolonged peripheral immunosuppressive responses as consequences of random amphetamine…The results indicate that the chronic and random AMPH exposure alone and the acute (single injection) challenge of the drug after the withdrawal phase induced long-term immunosuppressive effects, which were similar to those occurring during the stress response, and sensitized the peripheral immunosuppressive and corticosterone responses of the rat to the disinhibitory effects of this stressor.
Highlights
The drug addiction is a chronically relapsing disorder characterized by compulsive drug use and loss of control over drug intake (Kolokotroni et al 2012; Wemm and Sinha 2019)
In comparison with the control saline treated controls (SAL) and AMPH withdrawal groups, there was a significant decrease in the total blood leukocyte number after the AMPH chronic treatment alone and AMPH challenge after withdrawal (Tukey’s post hoc test)
The present study shows that the chronic, random AMPH treatment and the acute challenge of AMPH after the long-term withdrawal phase, were capable of significantly suppressing the peripheral inflammatory response, which clearly indicates the immune system activation in response to the drug exposure
Summary
The drug addiction is a chronically relapsing disorder characterized by compulsive drug use and loss of control over drug intake (Kolokotroni et al 2012; Wemm and Sinha 2019). AMPH has the capacity to modulate immune cells resulting in the drug long-term effects which may manifests as a neuropsychiatric disorder and that increases susceptibility to such diseases as HIV, infections (Freire-Garabal et al 1999) as well as tumors (Freire-Garabal et al 1992). We previously reported (Wrona et al 2005) that single AMPH injection (1 mg/kg b.w., i.p.) in rats increased blood NK cell number and cytotoxic activity accompanied by lymphopenia, neutrocytosis, monocytosis, and an increased plasma corticosterone concentration. This immunostimulative AMPH-induced effect on anti-tumor activity of NK cells was dependent on beta-adrenergic mechanism (Glac et al 2006). The T CD4+/TCD8+ lymphocyte ratio in blood is used in the diagnosis of HIV infections (Pahwa et al 2008), hepatitis C virus (Viso et al 2007) and autoimmune disorders (Pichler et al 2009)
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