Enduring effects of methylphenidate: the role played by route of drug administration

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University of New Brunswick


Methylphenidate (MPD; Ritalin®) is a psychostimulant used to treat attention deficit/hyperactivity disorder. In rodents, chronic treatment with MPD via intraperitoneal (IP) injection during adolescence results in both neurochemical and behavioral indices of depression during adulthood; however, in clinical practice, MPD is administered orally. Drug effects can vary widely depending on mode of administration, and therefore it is necessary to determine if oral treatment with MPD also enhances modeled depression. Experiment 1 investigated blood plasma levels of MPD following both oral and IP administration to male Sprague-Dawley rats. The quantitative plasma results demonstrated that 2 mg/kg IP and 5 mg/kg oral MPD resulted in equivalent and clinically relevant levels of systemic MPD. Experiment 2 investigated the enduring effects of both IP and oral chronic MPD on two of the hallmark symptoms of depression (anhedonia and behavioral despair) and a measure of anxiety. The current study showed that in the sucrose preference test and the forced swim test (measures of anhedonia and behavioral despair, respectively), MPD resulted in more depressive-like behaviours, independent of mode of administration. MPD effects on anxiety (as measured by the elevated-plus maze) were dependent upon mode of administration. IP administration of MPD resulted in significantly higher levels of anxiety compared to oral administration of MPD. The results of this study indicated that different mode of administrations can alter research findings, resulting in vastly different conclusions. This finding is important given the penchant of preclinical studies for using IP administration, regardless of the mode of administration used clinically. The current study's finding that both oral and IP chronic MPD treatment during adolescences resulted in an increase in symptoms of behavioral despair in adulthood highlights the need for further research to improve our understanding of the potentially enduring effects resulting from early-life MPD exposure.