Methamphetamine binge administration dose ‐dependently enhanced negative affect and voluntary drug consumption in rats following prolonged withdrawal: role of hippocampal FADD

This study evaluated the long‐term consequences of binge methamphetamine administration (three pulses/day, every 3 hours, 4 days, i.p.; dose–response: 2.5, 5 and 7.5 mg/kg) in adult Sprague–Dawley rats at two behavioral levels following 25 days of withdrawal: (1) negative affect (behavioral despair—forced‐swim test, and anhedonia—1% sucrose consumption, two‐bottle choice test) and (2) voluntary methamphetamine consumption (20 mg/l, two‐bottle choice test). Striatal and hippocampal brain samples were dissected to quantify monoamines content by high‐performance liquid chromatography and to evaluate neurotoxicity (dopaminergic and serotonergic markers) and neuroplasticity markers [i.e. cell fate regulator (Fas‐associated protein with death domain) FADD] by Western blot. The results showed that methamphetamine administration induced dose‐dependent negative effects during prolonged withdrawal in adult rats. In particular, rats treated repeatedly with methamphetamine (7.5 mg/kg) showed (1) enhanced negative affect—increased anhedonia associated with behavioral despair, (2) increased voluntary methamphetamine consumption, (3) enhanced neurotoxicity—decreased dopamine and metabolites in striatum and decreased serotonin in hippocampus, (4) altered neuroplasticity markers—decreased FADD protein and increased p‐FADD/FADD balance selectively in hippocampus and (5) higher consumption rates of methamphetamine that were associated with lower FADD content ...
Source: Addiction Biology - Category: Addiction Authors: Tags: Original Article Source Type: research