BackgroundA hallmark of psychostimulants is the persistence of neurobiological changes they produce. The difficulty in reversing long-time effects of psychostimulants use is why addiction therapy is so ineffective. This study aimed to look for such drug-induced changes that can be detected even after many weeks of abstinence.MethodsRats were given 12 doses of amphetamine (Amph) at 1.5 mg/kg. The rewarding effect of Amph was assessed using ultrasonic vocalization. After 14 and 28 days of abstinence, tissue levels of dopamine (DA), serotonin (5-HT), and their metabolites were measured in the prefrontal cortex (PFC), nucleus accumbens (Acb), dorsomedial (CPuM), and dorsolateral (CPuL) striatum.ResultsAfter 28 days of abstinence, DA levels were increased in the dorsal striatum while 5-HT levels were decreased in all brain regions studied. The opposite direction of changes in DA and 5-HT tissue levels observed in the dorsal striatum may be related to the changes in the emotional state during abstinence and may contribute to the incubation of craving and relapses. Tissue levels of 5-HT and DA showed intra- and inter-structural correlations, most pronounced after 14 days of abstinence. Most of them were absent in the control group (ctrl), which may indicate that their appearance was related to the changes induced by earlier Amph administration. We did not find any associations between reward sensitivity and the persistence of Amph-induced neurochemical disturbances.ConclusionsAdministration of 12 moderate doses of Amph causes prolonged changes in DA and 5-HT tissue levels. The direction and severity of the changes are dependent on the brain region and the neurotransmitter studied.