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Pre-clinical evidence that methylphenidate increases motivation and/or reward preference to search for high value rewards

LN. Pulido, JA. Pochapski, A. Sugi, JY. Esaki, JL. Stresser, WN. Sanchez, G. Baltazar, D. Levcik, R. Fuentes, C. Da Cunha

. 2023 ; 437 (-) : 114065. [pub] 20220828

Language English Country Netherlands

Document type Journal Article

Methylphenidate is a stimulant used to treat attention deficit and hyperactivity disorder (ADHD). In the last decade, illicit use of methylphenidate has increased among healthy young adults, who consume the drug under the assumption that it will improve cognitive performance. However, the studies that aimed to assess the methylphenidate effects on memory are not consistent. Here, we tested whether the effect of methylphenidate on a spatial memory task can be explained as a motivational and/or a reward effect. We tested the effects of acute and chronic i.p. administration of 0.3, 1 or 3 mg/kg of methylphenidate on motivation, learning and memory by using the 8-arm radial maze task. Adult male Wistar rats learned that 3 of the 8 arms of the maze were consistently baited with 1, 3, or 6 sucrose pellets, and the number of entries and reentries into reinforced and non-reinforced arms of the maze were scored. Neither acute nor chronic (20 days) methylphenidate treatment affected the number of entries in the non-baited arms. However, chronic, but not acute, 1-3 mg/kg methylphenidate increased the number of reentries in the higher reward arms, which suggests a motivational/rewarding effect rather than a working memory deficit. In agreement with this hypothesis, the methylphenidate treatment also decreased the approach latency to the higher reward arms, increased the approach latency to the low reward arm, and increased the time spent in the high, but not low, reward arm. These findings suggest that methylphenidate may act more as a motivational enhancer rather than a cognitive enhancer in healthy people.

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$a Methylphenidate is a stimulant used to treat attention deficit and hyperactivity disorder (ADHD). In the last decade, illicit use of methylphenidate has increased among healthy young adults, who consume the drug under the assumption that it will improve cognitive performance. However, the studies that aimed to assess the methylphenidate effects on memory are not consistent. Here, we tested whether the effect of methylphenidate on a spatial memory task can be explained as a motivational and/or a reward effect. We tested the effects of acute and chronic i.p. administration of 0.3, 1 or 3 mg/kg of methylphenidate on motivation, learning and memory by using the 8-arm radial maze task. Adult male Wistar rats learned that 3 of the 8 arms of the maze were consistently baited with 1, 3, or 6 sucrose pellets, and the number of entries and reentries into reinforced and non-reinforced arms of the maze were scored. Neither acute nor chronic (20 days) methylphenidate treatment affected the number of entries in the non-baited arms. However, chronic, but not acute, 1-3 mg/kg methylphenidate increased the number of reentries in the higher reward arms, which suggests a motivational/rewarding effect rather than a working memory deficit. In agreement with this hypothesis, the methylphenidate treatment also decreased the approach latency to the higher reward arms, increased the approach latency to the low reward arm, and increased the time spent in the high, but not low, reward arm. These findings suggest that methylphenidate may act more as a motivational enhancer rather than a cognitive enhancer in healthy people.
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$a Pochapski, Jose A $u Laboratorio de Fisiologia e Farmacologia do Sistema Nervoso Central, Department of Pharmacology, Universidade Federal do Parana, Curitiba, Brazil; Department of Biochemistry, Universidade Federal do Parana, Curitiba, Brazil
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$a Sugi, Adam $u Laboratorio de Fisiologia e Farmacologia do Sistema Nervoso Central, Department of Pharmacology, Universidade Federal do Parana, Curitiba, Brazil; Department of Biochemistry, Universidade Federal do Parana, Curitiba, Brazil
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$a Esaki, Julie Y $u Laboratorio de Fisiologia e Farmacologia do Sistema Nervoso Central, Department of Pharmacology, Universidade Federal do Parana, Curitiba, Brazil
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$a Sanchez, William N $u Laboratorio de Fisiologia e Farmacologia do Sistema Nervoso Central, Department of Pharmacology, Universidade Federal do Parana, Curitiba, Brazil; Department of Biochemistry, Universidade Federal do Parana, Curitiba, Brazil; Integrative Neurobiology Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA
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$a Baltazar, Gabriel $u Laboratorio de Fisiologia e Farmacologia do Sistema Nervoso Central, Department of Pharmacology, Universidade Federal do Parana, Curitiba, Brazil; Department of Biochemistry, Universidade Federal do Parana, Curitiba, Brazil
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