Does repetitive Ritalin injection produce long-term effects on SD female adolescent rats?

Lee, Min J.; Peng, Yang; Wilcox, Victor T.; Burau, Keith D.; Swann, Alan C.; Dafny, Nachum

doi:10.1016/j.neuropharm.2009.06.008

Cited by 40 publications

(50 citation statements)

References 64 publications

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“…Activity is altered in a dose-dependent manner, with lowto-moderate doses producing activity above baseline for 1-3 h, although high doses (40 mg/kg) lead to a delayed onset of increased locomotor activity while animals first engage in stereotypic behavior (Gaytan et al, 1997). Daily injections for a week alter the amplitude, mean, and acrophase of activity rhythms (Lee et al, 2009(Lee et al, , 2011, although the findings of these studies lacked the temporal resolution for detecting the behavioral phenomena described here. Similarly to other amphetamines, methylphenidate has been shown to restore circadian rhythmicity to animals rendered arrhythmic with SCN lesions (Honma and Honma, 1992), although only when activity levels were double those observed during baseline.…”

Section: Discussionmentioning

confidence: 82%

Methylphenidate Modifies the Motion of the Circadian Clock

Antle

Diepen

Deboer

et al. 2012

Neuropsychopharmacol

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People with attention-deficit/hyperactivity disorder (ADHD) often experience sleep problems, and these are frequently exacerbated by the methylphenidate they take to manage their ADHD symptoms. Many of the changes to sleep are consistent with a change in the underlying circadian clock. The present study was designed to determine if methylphenidate alone could alter properties of the circadian clock. Young male mice were examined in light-dark cycles and in constant darkness and recordings were performed on behavioral activity, sleep, and electrical activity in the suprachiasmatic nucleus (SCN) of freely moving mice. Methylphenidate in the drinking water (0.08%) significantly increased activity in the mid-to-late night, and led to a delay in the onset of activity and sleep relative to the light-dark cycle. While locomotor levels returned to baseline after treatment ended, the phase angle of entrainment required at least a week to return to baseline levels. In constant darkness, the free-running period of both wheel-running and general locomotor rhythms was lengthened by methylphenidate. When the treatment ended, the free-running period either remained stable or only partially reverted to baseline levels. Methylphenidate also altered the electrical firing rate rhythms in the SCN. It induced a delay in the trough of the rhythm, an increment in rhythm amplitude, and a reduction in rhythm variability. These observations suggest that methylphenidate alters the underlying circadian clock. The observed changes are consistent with clock alterations that would promote sleep-onset insomnia.

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Section: Discussionmentioning

confidence: 82%

Methylphenidate Modifies the Motion of the Circadian Clock

Antle

Diepen

Deboer

et al. 2012

Neuropsychopharmacol

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“…These pioneering studies have yielded striking results, indicating that early life treatment with MPH may alter circadian rhythms, induce anxiety that persists into adulthood, and even impair object-recognition memory (Lee et al, 2009; Algahim et al, 2010). However, many of the studies have not been particularly stringent in their dosing regimens, and the reader must examine the amount of drug used in each study very carefully.…”

Section: Methylphenidate and The Developing Brainmentioning

confidence: 99%

Performance enhancement at the cost of potential brain plasticity: neural ramifications of nootropic drugs in the healthy developing brain

Urban

Gao

2014

Front. Syst. Neurosci.

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Cognitive enhancement is perhaps one of the most intriguing and controversial topics in neuroscience today. Currently, the main classes of drugs used as potential cognitive enhancers include psychostimulants (methylphenidate (MPH), amphetamine), but wakefulness-promoting agents (modafinil) and glutamate activators (ampakine) are also frequently used. Pharmacologically, substances that enhance the components of the memory/learning circuits—dopamine, glutamate (neuronal excitation), and/or norepinephrine—stand to improve brain function in healthy individuals beyond their baseline functioning. In particular, non-medical use of prescription stimulants such as MPH and illicit use of psychostimulants for cognitive enhancement have seen a recent rise among teens and young adults in schools and college campuses. However, this enhancement likely comes with a neuronal, as well as ethical, cost. Altering glutamate function via the use of psychostimulants may impair behavioral flexibility, leading to the development and/or potentiation of addictive behaviors. Furthermore, dopamine and norepinephrine do not display linear effects; instead, their modulation of cognitive and neuronal function maps on an inverted-U curve. Healthy individuals run the risk of pushing themselves beyond optimal levels into hyperdopaminergic and hypernoradrenergic states, thus vitiating the very behaviors they are striving to improve. Finally, recent studies have begun to highlight potential damaging effects of stimulant exposure in healthy juveniles. This review explains how the main classes of cognitive enhancing drugs affect the learning and memory circuits, and highlights the potential risks and concerns in healthy individuals, particularly juveniles and adolescents. We emphasize the performance enhancement at the potential cost of brain plasticity that is associated with the neural ramifications of nootropic drugs in the healthy developing brain.

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“…Tolerance to a drug refers to drug induced adaptations that lead to attenuating effects when the same dose of that drug is given again; to get the same effect, a higher dose is required. Alternatively, behavioral sensitization is a progressive amplification of behavioral responses to repeated psychostimulant exposure (Chao and Nestler, 2004; Dafny and Yang 2006; Gaytan et al, 1996; Kalivas et al, 1988; Lee et al, 2009; Robinson 1984; Wolf 1988; Yang et al, 2003, 2011). Behavioral tolerance and sensitization are experimental markers used to indicate the potential of a psychostimulant to elicit drug dependence.…”

Section: Introductionmentioning

confidence: 99%

Acute and chronic dose–response effect of methylphenidate on ventral tegmental area neurons correlated with animal behavior

Jones

Dafny²

2013

J Neural Transm

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Methylphenidate (MPD) is used to treat ADHD and as a cognitive enhancement and recreationally. MPD's effects are not fully understood. One of the sites of psychostimulant action is the ventral tegmental area (VTA). The VTA neuronal activity was recorded from freely behaving rats using a wireless system. 51 animals were divided into groups: saline, 0.6, 2.5, and 10.0 mg/kg MPD. The same repetitive MPD dose can elicit either behavioral sensitization or tolerance, thus the evaluation of the VTA neuronal activity was based on the animals’ behavioral response to chronic MPD exposure: animals exhibiting behavioral tolerance or sensitization. Acute MPD elicits dose related increases in behavioral activity. About half of the animals exhibited behavioral sensitization or tolerance to each of the MPD doses. 361 units were recorded from the VTA and exhibited similar spike shape on experimental day 1 (ED1) and on ED10. 71%, 84%, and 79% of VTA units responded to acute 0.6, 2.5, and 10.0 mg/kg MPD respectively. The neuronal baseline activity at ED10 was significantly modified in 94%, 95%, and 100% of VTA units following 0.6, 2.5 and 10.0 mg/kg MPD respectively. Following chronic MPD exposure, 91%, 98%, and 100% exhibit either electrophysiological tolerance or sensitization of 0.6, 2.6, or 10.0 mg/kg MPD respectively. In conclusion, the chronic administration of the same dose of MPD caused some animals to exhibit behavioral sensitization and other animals to exhibit tolerance. The VTA units recorded from animals exhibiting behavioral sensitization responded significantly differently to MPD from animals that exhibited behavioral tolerance.

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Does repetitive Ritalin injection produce long-term effects on SD female adolescent rats?

Cited by 40 publications

References 64 publications

Methylphenidate Modifies the Motion of the Circadian Clock

Methylphenidate Modifies the Motion of the Circadian Clock

Performance enhancement at the cost of potential brain plasticity: neural ramifications of nootropic drugs in the healthy developing brain

Acute and chronic dose–response effect of methylphenidate on ventral tegmental area neurons correlated with animal behavior

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