Methylphenidate Preferentially Increases Catecholamine Neurotransmission within the Prefrontal Cortex at Low Doses that Enhance Cognitive Function

Berridge, Craig W.; Devilbiss, David M.; Andrzejewski, Matthew E.; Arnsten, Amy F.T.; Kelley, Ann E.; Schmeichel, Brooke E.; Hamilton, C.J.; Spencer, Robert C.

doi:10.1016/j.biopsych.2006.04.022

Cited by 537 publications

(604 citation statements)

References 45 publications

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“…One possible explanation could be a different profile of norepinephrine response. In fact, ( + )-methamphetamine (also referred as d-methamphetamine, the stereoisomer used in the present study) has been shown to be a poor NE releaser (Kuczenski et al, 1995), whereas methylphenidate is very effective at increasing the extracellular levels of NE in different brain areas (Kuczenski and Segal, 2002;Berridge et al, 2006).…”

Section: Figurementioning

confidence: 69%

5-HT1B Receptor-Mediated Serotoninergic Modulation of Methylphenidate-Induced Locomotor Activation in Rats

Borycz

Zapata

Quiroz

et al. 2007

Neuropsychopharmacol

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Previous studies have shown that the dopamine (DA) uptake blocker methylphenidate, a psychostimulant widely used for the treatment of attention-deficit hyperactivity disorder (ADHD), prevents the neurotoxic effects of the highly abused DA releaser methamphetamine. However, there is a lack of information about the pharmacological interactions of these two drugs at the behavioral level. When systemically administered within an interval of 2 h, previous administration of methylphenidate (10 mg/kg, intraperitoneal (i.p.)) did not modify locomotor activation induced by methamphetamine. On the other hand, previous administration of methamphetamine (1 mg/kg, i.p.) markedly potentiated methylphenidate-induced motor activation. With in vivo microdialysis experiments, methamphetamine and methylphenidate were found to increase DA extracellular levels in the nucleus accumbens (NAs). Methamphetamine, but not methylphenidate, significantly increased the extracellular levels of serotonin (5-HT) in the NAs. Methamphetamine-induced 5-HT release remained significantly elevated for more than 2 h after its administration, suggesting that the increased 5-HT could be responsible for the potentiation of methylphenidate-induced locomotor activation. In fact, previous administration of the 5-HT uptake blocker fluoxetine (10 mg/kg, i.p.) also potentiated the motor activation induced by methylphenidate. A selective 5-HT 1B receptor antagonist (GR 55562; 1 mg/kg), but not a 5-HT 2 receptor antagonist (ritanserin; 2 mg/kg, i.p.), counteracted the effects of methamphetamine and fluoxetine on the motor activation induced by methylphenidate. Furthermore, a 5-HT 1B receptor agonist (CP 94253; 1-10 mg/kg, i.p.) strongly and dose-dependently potentiated methylphenidate-induced locomotor activation. The 5-HT 1B receptor-mediated modulation of methylphenidate-induced locomotor activation in rat could have implications for the treatment of ADHD.

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Section: Figurementioning

confidence: 69%

5-HT1B Receptor-Mediated Serotoninergic Modulation of Methylphenidate-Induced Locomotor Activation in Rats

Borycz

Zapata

Quiroz

et al. 2007

Neuropsychopharmacol

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“…In nonsocial domains, task performance related to the same fronto-striatal circuitry is known to be sensitive to levels of catecholamine activity (Berridge, 2007;Clatworthy et al, 2009;Cools et al, 2001;Del Campo et al, 2011;Robbins and Arnsten, 2009), but catecholamine mediation of conformity of value has not yet been established. Methylphenidate (MPH) is an indirect catecholamine agonist that increases extracellular dopamine and noradrenalin levels in the brain (Berridge et al, 2006;Volkow et al, 2001) with consequences for learning and other cognitions. With respect to value, MPH can enhance phasic dopamine responses to external stimuli and associated interest in rewards and tasks (Volkow et al, 2002(Volkow et al, , 2004, modulate flexible adaptation of stimulus-reinforcement association (Clatworthy et al, 2009), and alter reinforcement-associated synaptic plasticity and behavior (Tye et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Modulation of Social Influence by Methylphenidate

Campbell-Meiklejohn

Simonsen

Jensen

et al. 2012

Neuropsychopharmacol

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The ability to infer value from the reactions of other people is a common and essential ability with a poorly understood neurobiology. Commonly, social learning matches one's values and behavior to what is perceived as normal for one's social group. This is known as conformity. Conformity of value correlates with neural activity shared by cognitions that depend on optimum catecholamine levels, but catecholamine involvement in conformity has not been tested empirically. Methylphenidate (MPH) is an indirect dopamine and noradrenalin agonist, commonly used for the treatment of attention-deficit hyperactivity disorder for which it reduces undesirable behavior as evaluated by peers and authority figures, indicative of increased conformity. We hypothesized that MPH might increase conformity of value. In all, 38 healthy adult females received either a single oral 20 mg dose of MPH or placebo (PL). Each subject rated 153 faces for trustworthiness followed immediately by the face's mean rating from a group of peers. After 30 min and a 2-back continuousperformance working-memory task, subjects were unexpectedly asked to rate all the faces again. Both the groups tended to change their ratings towards the social norm. The MPH group exhibited twice the conformity effect of the PL group following moderate social conflict, but this did not occur following large conflicts. This suggests that MPH might enhance signals that would otherwise be too weak to evoke conformity. MPH did not affect 2-back performance. We provide a new working hypothesis of a neurocognitive mechanism by which MPH reduces socially disruptive behavior and provides novel evidence of catecholamine mediation of social learning.

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“…Since the subjects in Experiment 1 were less motivated due to the fed condition compared to Experiment 2, (food restriction = higher motivation/arousal), enhanced attention to the maze may have played a bigger role in Experiment 1 compared to Experiment 2. Berridge et al [3], have demonstrated that low oral doses of MPD increase norepinephrine and dopamine release in prefrontal cortex, a finding which is consistent with an effect on attention and working memory, two functions which rely on an intact prefrontal cortex. The RAM is designed as a test of spatial working memory.…”

Section: Discussionmentioning

confidence: 76%

“…That is, only a few papers have reported on the effects of MPD in adult rats on various cognitive tests (e.g. [3]). Arnsten & Dudley [1] reported that MPD improved performance in young adult male rats on a task which was dependent upon the prefrontal cortex.…”

Section: Discussionmentioning

confidence: 99%

“…They also found that these doses of MPD increased extracellular norepinephrine in the hippocampus and had little effect on dopamine levels in the nucleus accumbens, further suggesting that low MPD doses produce neurochemical changes which are distinct from higher doses which have relatively greater effects on the DA system. Recently there have been reports of the effects of low doses of oral MPD on behavior including Arnsten & Dudley [1] and Berridge et al [3]. Central components of cognitive function, sustained attention and working memory, were found to be improved by low doses of MPD.…”

Section: Introductionmentioning

confidence: 99%

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Methylphenidate improves performance on the radial arm maze in periadolescent rats

Dow-Edwards

Weedon

Hellmann

2008

Neurotoxicology and Teratology

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Methylphenidate (Ritalin; MPD) is one of the most commonly prescribed drugs in childhood and adolescence and many clinical studies have documented its efficacy. Due to the limitations of conducting invasive research in humans, animal models can be beneficial for studying drug effects. However, few animal studies have demonstrated the effects of methylphenidate on cognitive processes. The objective of this study was to find a dose of methylphenidate that was effective in improving performance on a spatial working memory cognitive task when administered orally to periadolescent rats. Therefore, we dosed subjects with methylphenidate at 1 or 3 mg/kg/day via gastric intubation from postnatal day 22 to 59 and assessed the effects of the drug on performance on the radial arm maze each day. To enhance performance overall, a second experiment was conducted where the subjects were moderately food restricted (to 90% of the free-feeding weight). Results of Experiment 1 show that during the first week of testing only the 3mg/kg MPD-treated males showed improved performance (entries prior to repeated entry) when ad-lib fed and housed in pairs while the same dose significantly improved performance in both males and females under conditions of food-restriction and individual housing in Experiment 2. MPD also produced a pattern of increased errors and arms entered during the first week, especially in Experiment 2. MPD increased locomotor activity when tested at postnatal day 60 in both experiments. The data suggest that 3mg/ kg oral methylphenidate improves performance on a spatial cognitive task only early in treatment in the rat. While males show improvement under conditions of both high and low motivation, females only show MPD effects when highly motivated. Hypothetically, methylphenidate may improve radial arm maze performance through increased attention and improved spatial working memory and/or alterations in locomotion, reactivity to novelty or anxiety. Regardless, the study supports the utility of the rat as a suitable model to examine the effects of low dose oral MPD.

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Methylphenidate Preferentially Increases Catecholamine Neurotransmission within the Prefrontal Cortex at Low Doses that Enhance Cognitive Function

Cited by 537 publications

References 45 publications

5-HT1B Receptor-Mediated Serotoninergic Modulation of Methylphenidate-Induced Locomotor Activation in Rats

5-HT1B Receptor-Mediated Serotoninergic Modulation of Methylphenidate-Induced Locomotor Activation in Rats

Modulation of Social Influence by Methylphenidate

Methylphenidate improves performance on the radial arm maze in periadolescent rats

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