Cognitive effects of methamphetamine and amphetamine withdrawal in rodents: a systematic review

Background Methamphetamine (METH) and amphetamine (AMPH) are widely misused psychostimulants that induce enduring alterations in brain function and behavior, including cognitive impairment. To date, literature in this area has not been sufficiently reviewed and summarized to account for how methodological variables, such as dosage and administration contingency, influence cognitive outcomes. Objective This systematic review evaluates the effects of METH and AMPH withdrawal on rodent cognition, with particular attention to how outcomes are influenced by dose, sex, strain, and withdrawal duration. Methods A systematic search of Web of Science, PubMed, Scopus, and OVID was conducted following PRISMA 2020 guidelines. Eligible studies were full-text, English-language articles assessing cognition in rodents after withdrawal from METH or AMPH. Risk of bias was evaluated using SYRCLE’s tool. Ultimately, 37 original articles published between 1971 and 2025 were included in this review. Results Withdrawal impaired recognition and non-spatial working memory (novel object recognition and temporal order) as well as spatial working memory (Morris Water Maze, object placement recognition, Y-maze, radial arm maze, and T-maze). Outcomes varied according to dose, withdrawal duration, sex, and strain. Some studies reported partial recovery or even enhanced reversal learning with prolonged abstinence. Extended-access and high-dose regimens produced more persistent deficits, with females generally more vulnerable than males. Locomotor findings were inconsistent: some studies reported hypoactivity or impaired motor coordination, while others observed no change. Conclusion Rodent evidence indicates that METH and AMPH withdrawal most reliably disrupt recognition and working memory, with less consistent effects on spatial learning and locomotion. Standardization of dosing regimens, withdrawal periods, and behavioral tasks is needed to improve reproducibility and enhance translational relevance to human addiction research.