DOSE-DEPENDENT EFFECTS OF METHAMPHETAMINE ON NEUROCHEMICAL AND NEUROIMMUNE MARKERS IN THE BRAIN, SPLEEN, AND KIDNEY

Objective: This study evaluated the effects of low, moderate, and high methamphetamine (METH) doses on noradrenaline (NA), dopamine (DA), vesicular monoamine transporter type 2 (VMAT-2), and toll-like receptor 4 (TLR-4) in central and peripheral nervous systems(PNS) of lymphoid and non-lymphoid organs. Methods: A total of 120 Balb/c male mice (8–9 weeks) were divided into four groups (n=30). Three groups received intraperitoneal METH injections (2 mg/g, 5 mg/g, 10 mg/g), while the control received saline. Subgroups (n=10) were sacrificed at 1 week, 2 weeks, or after a 7 days withdrawal. Brain central nervous system (CNS), spleen (lymphoid), and kidney (non-lymphoid) tissues were homogenized, and supernatants analyzed for DA, NA, VMAT-2, and TLR-4 using ELISA kits. Results: NA, DA, VMAT-2, and TLR-4 levels significantly (p< 0.05) increased in all METH-treated groups compared with control, in a dose- and time-dependent manner. After 7 days withdrawal, Group 1 (2 mg/g) values normalized, whereas Group 2 (5 mg/g) remained elevated versus control. All Group 3 (10 mg/g) mice died during withdrawal,because a high dose is synergistic central and peripheral toxicity Conclusion: Low-dose METH-induced alterations may resolve upon cessation, suggesting reversible effects. Moderate doses cause persistent damage requiring intervention, while high doses lead to severe withdrawal and mortality. Importantly, METH effects extend beyond the CNS to peripheral systems, impacting both lymphoid and non-lymphoid organs.