Methylphenidate improves cue navigation in the Morris water maze in rats

Zeise, Marc L.; Espinoza, Sergio G.; González, Adolfo; Cerda, Fernanda S.; Nacarate, Judith; Yáñez, Cesar G.; Morales, Bernardo

doi:10.1097/wnr.0b013e32819f8f3f

Cited by 14 publications

(8 citation statements)

References 13 publications

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“…The control subjects may "catch up" to the treated subjects once their presumed fear of being on the open arms is overcome. MPD at low oral doses has been found to reduce thigmotaxis, a measure of anxiety in the Morris water maze [32]. In that study, after the first few sessions of testing, there were no differences between MPD-treatment and controls, a finding which parallels our overall results quite well.…”

Section: Discussionsupporting

confidence: 83%

“…However, the 3mg/kg dose has been shown to decrease locomotor activity [11] when quantified in the home cage in adult male rats. Also a recent study by Zeise et al [32] found improvements on the Morris water maze following oral dosing of MPD to preadolescent rats which were not due to increased swim speed. In addition, examination of the arms entered during the first week of testing revealed that there were no significant differences between the MPD 3 group and the controls suggesting that the drug did not produce non-specific increases in activity on the maze.…”

Section: Discussionmentioning

confidence: 94%

“…While possible, the pattern of errors made would suggest that enhanced motivation to obtain a reward, enhanced attention and/or enhanced spatial working memory were greater factors. Low dose MPD has also been shown to enhance goal-directed behavior without improving learning per se [32].…”

Section: Discussionmentioning

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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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 94%

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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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“…Surprisingly few studies have examined the long-term effects of chronic MPH exposure on cognition using No effect on monoamine levels or patterns of c-fos expression in striatum or prefrontal cortex ; no effect on locomotor activity Lagace et al (2006) PND 20, rats 2 mg/kg i.p., 16 d 12-78 d Decreased hippocampal neurogenesis at adulthood ; increased plasma corticosterone but no effect on cell proliferation ; no effect on locomotion LeBlanc-Duchin & Taukulis (2007) PND (Scherer et al 2010 ;Zeise et al 2007 ;Zhu et al 2007) (see Table 1). Impairments in spatial reference and working memory were linked to decreased BDNF levels and increased acetylcholinesterase activity in PFC, but not hippocampus (Scherer et al 2010).…”

Section: Mph Effects On Cognitive Processesmentioning

confidence: 94%

Cognitive and emotional behavioural changes associated with methylphenidate treatment: a review of preclinical studies

Britton

2011

Int. J. Neuropsychopharm.

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There is evidence from animal studies that repeated exposure to methylphenidate (MPH), a widely used psychostimulant for the treatment of attention deficit hyperactivity disorder (ADHD), produces behavioural, structural and neurochemical changes that persist long after drug administration has ended. However, the translational utility of much of this work is compromised by the use of drug doses and routes of administration that produce plasma and brain MPH levels that fall outside the clinical range, i.e. experimental parameters more relevant to drug abuse than ADHD. We used PubMed to identify pre-clinical studies that employed repeated MPH administration at low doses in young rodents and examined long-term effects on cognition, emotion, and brain structure and function. A review of this work suggests that repeated MPH treatment during early development can modify a number of cognitive, behavioural and brain processes, but these are reduced when low therapeutic doses are employed. Moreover, MPH sites of action extend beyond those implicated in ADHD. Studies that combined neurobiological and behavioural approaches provide important insights into the mechanisms underlying MPH-produced effects on cognitive and behavioural processes, which may be relevant to MPH therapeutic efficacy. There is an emerging consensus that pharmacological treatment of childhood psychiatric disorders produces persistent neuroadaptations, highlighting the need for studies that assess long-term effects of early developmental pharmacotherapy. In this regard, studies that mimic clinical therapy with rodents are useful experimental approaches for defining the behavioural and neural plasticity associated with stimulant therapy in paediatric populations.

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“…Increasingly, MPH is being used both on and off-label to specifically improve long-term memory (LTM) [2][3][4]. Few studies, however, have examined MPH's ability to modulate spatial or long-term memory [5][6][7]. Rather, most research has focused on MPH-induced improvements in working memory, attention, and cognitive control [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Methylphenidate enhances acquisition and retention of spatial memory

Carmack¹,

Block²,

Howell³

et al. 2014

Neuroscience Letters

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h i g h l i g h t s• 10 mg/kg MPH given pre-training enhances learning on the hidden platform version of the Morris water maze.• 1 or 10 mg/kg MPH given pre-training enhances retention of spatial memory in the water maze.• 10 mg/kg MPH given chronically before Pavlovian fear conditioning dramatically impairs long-term fear memory. Psychostimulants containing methylphenidate (MPH) are increasingly being used both on and off-label to enhance learning and memory. Still, almost no studies have investigated MPH's ability to specifically improve spatial or long-term memory. Here we examined the effect of training with 1 or 10 mg/kg MPH on hidden platform learning in the Morris water maze. 10 mg/kg MPH improved memory acquisition and retention, while 1 mg/kg MPH improved memory retention. Taken together with prior evidence that low, clinically relevant, doses of MPH (0.01-1 mg/kg MPH) enhance fear memory we conclude that MPH broadly enhances memory. a r t i c l e i n f o

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Methylphenidate improves cue navigation in the Morris water maze in rats

Cited by 14 publications

References 13 publications

Methylphenidate improves performance on the radial arm maze in periadolescent rats

Methylphenidate improves performance on the radial arm maze in periadolescent rats

Cognitive and emotional behavioural changes associated with methylphenidate treatment: a review of preclinical studies

Methylphenidate enhances acquisition and retention of spatial memory

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