A novel method for oral stimulant administration in the neonate rat and similar species

Wheeler, Tracey; Eppolito, Amy K.; Smith, Liane; Huff, Thomas B.; Smith, Robert F.

doi:10.1016/j.jneumeth.2006.07.019

Cited by 27 publications

(17 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The MPH administration was oral, further modeling the human exposure. In addition to the modeling parameters described above, the 3 mg/kg dose resulted in MPH serum levels similar to those described for the clinical range of children [Greenhill et al, 2001;Quinn et al, 2004;Teicher et al, 2006;Quinn et al, 2007] and adolescent rats using oral treatment (2-5 mg MPH/kg) [Wheeler et al, 2007]. MPH serum levels of female rats were higher than those of males, a sex effect previously described [Bakhtiar and Tse 2003].…”

Section: Discussionsupporting

confidence: 71%

Flow cytometric detection of Pig‐A mutant red blood cells using an erythroid‐specific antibody: Application of the method for evaluating the in vivo genotoxicity of methylphenidate in adolescent rats

Dobrovolsky

Boctor

Twaddle

et al. 2009

Environ and Mol Mutagen

View full text Add to dashboard Cite

A modified flow cytometry assay for Pig-A mutant rat red blood cells (RBCs) was developed using an antibody that positively identifies rat RBCs (monoclonal antibody HIS49). The assay was used in conjunction with a flow cytometric micronucleus (MN) assay to evaluate gene mutation and clastogenicity/aneugenicity in adolescent male and female rats treated with methylphenidate hydrochloride (MPH). Sprague-Dawley rats were treated orally with 3 mg/kg MPH (70/sex) or water (40/sex) 3 x /day on postnatal days (PNDs) 29-50. Eight additional rats (4/sex) were injected i.p. with N-ethyl-N-nitrosourea (ENU) on PND 28. Blood was collected on PNDs 29, 50, and 90, and used for determining serum MPH levels and/or conducting genotoxicity assays. On the first and last days of MPH treatment (PNDs 29 and 50), serum MPH levels averaged 21 pg/microl, well within the clinical treatment range. Relative to our previously published method (Miura et al. [2008]; Environ Mol Mutagen 49: 614-629), the HIS49 Pig-A mutation assay significantly reduced the background RBC mutant frequency; in the experiments with ENU-treated rats, the modification increased the overall sensitivity of the assay 2-3 fold. Even with the increased assay sensitivity, the 21 consecutive days of MPH treatment produced no evidence of Pig-A mutation induction (measured at PND 90); in addition, MPH treatment did not increase MN frequency (measured at PND 50). These results support the consensus view that the genotoxicity of MPH in pediatric patients reported earlier (El-Zein et al. [2005]: Cancer Lett 230: 284-291) cannot be reproduced in animal models, suggesting that MPH at clinically relevant levels may be nongenotoxic in humans.

show abstract

Section: Discussionsupporting

confidence: 71%

Flow cytometric detection of Pig‐A mutant red blood cells using an erythroid‐specific antibody: Application of the method for evaluating the in vivo genotoxicity of methylphenidate in adolescent rats

Dobrovolsky

Boctor

Twaddle

et al. 2009

Environ and Mol Mutagen

View full text Add to dashboard Cite

show abstract

“…The solution was administered with a micropipette. We placed the filled tip in or near the animal's mouth and slowly discharged the suspension to allow the animal to drink (Wheeler et al, 2007). The control rats were administrated with vehicle comprising 10% sucrose solution, in their appropriate volume (e.g.…”

Section: Mph Treatmentmentioning

confidence: 99%

Methylphenidate and environmental enrichment ameliorate the deleterious effects of prenatal stress on attention functioning

Zubedat

Aga-Mizrachi

Cymerblit‐Sabba

et al. 2015

Stress

View full text Add to dashboard Cite

Either pre- or post-natal environmental factors seem to play a key role in brain and behavioral development and to exert long-term effects. Increasing evidence suggests that exposure to prenatal stress (PS) leads to motor and learning deficits and elevated anxiety, while enriched environment (EE) shows protective effects. The dopaminergic system is also sensitive to environmental life circumstances and affects attention functioning, which serves as the preliminary gate to cognitive processes. However, the effects of methylphenidate (MPH) on the dopaminergic system and attentional functioning, in the context of these life experiences, remain unclear. Therefore, we aimed to examine the effects of EE or PS on distinct types of attention, along with possible effects of MPH exposure. We found that PS impaired selective attention as well as partial sustained attention, while EE had beneficial effects. Both EE and MPH ameliorated the deleterious effects of PS on attention functioning. Considering the possible psychostimulant effect of MPH, we examined both anxiety-like behavior as well as motor learning. We found that PS had a clear anxiogenic effect, whereas EE had an anxiolytic effect. Nevertheless, the treatment with both MPH and/or EE recovered the deleterious effects of PS. In the motor-learning task, the PS group showed superior performance while MPH led to impaired motor learning. Performance decrements were prevented in both the PS + MPH and EE + MPH groups. This study provides evidence that peripubertal exposure to EE (by providing enhanced sensory, motor, and social opportunities) or MPH treatments might be an optional therapeutic intervention in preventing the PS long-term adverse consequences.

show abstract

“…Given one of the main sources for MPH as a cognitive enhancer is likely to be the ADHD prescribed medication it is appropriate to use similar doses in the present study. It has also been demonstrated that this level can be achieved in rats using the same method of oral administration in apple juice employed here with doses between 1 mg/kg (9.56 ng/ml) and 5 mg/kg (36.61 ng/ml) (Wheeler et al, 2007). These levels were reached 15 min after administration, allowing time for the blood plasma levels to peak (Patrick et al, 1984), and around 5 min before effects on neurotransmitter levels have been shown to peak after oral administration (Kuczenski and Segal, 2002; Berridge et al, 2006).…”

Section: Methodsmentioning

confidence: 79%

“…This method removes the ethical and welfare concerns of repeated gavage and closely replicates the method of administration in humans (Wheeler et al, 2007). In addition, once trained the animals easily receive the juice even after long periods without administration.…”

Section: Methodsmentioning

confidence: 98%

The effects of methylphenidate on cognitive performance of healthy male rats

Rostron¹,

Kaplan²,

Gaeta³

et al. 2013

Front. Neurosci.

View full text Add to dashboard Cite

We aimed to investigate the effects of methylphenidate (MPH) in healthy rats on two distinct radial maze tasks which rely on brain structures and neurotransmitters known to be affected by MPH: the Random Foraging Non-Delay Task (RFNDT) and the Delayed Spatial Win Shift Task (DSWT). Hooded Lister rats were trained to complete either the RFNDT or the DSWT having received oral treatment of either a vehicle or MPH (3.0 mg/kg and 5.0 mg/kg for RFNDT, 3.0 mg/kg for DSWT). We found no effect of MPH on the RFNDT relative to the control group. However, those treated with 5.0 mg/kg MPH did take significantly longer to reach criterion performance than those treated with the 3.0 mg/kg MPH, suggesting some doses of MPH can have detrimental effects. For the DSWT, if MPH was present in both phases, performance did not differ from when it was absent in both phases. However, when present in only one phase there was an increase in errors made, although this only reached significance for when MPH was present only in the test-phase. These data suggest that MPH may have detrimental effects on task performance and can result in state-dependent effects in healthy individuals.

show abstract

A novel method for oral stimulant administration in the neonate rat and similar species

Cited by 27 publications

References 17 publications

Flow cytometric detection of Pig‐A mutant red blood cells using an erythroid‐specific antibody: Application of the method for evaluating the in vivo genotoxicity of methylphenidate in adolescent rats

Flow cytometric detection of Pig‐A mutant red blood cells using an erythroid‐specific antibody: Application of the method for evaluating the in vivo genotoxicity of methylphenidate in adolescent rats

Methylphenidate and environmental enrichment ameliorate the deleterious effects of prenatal stress on attention functioning

The effects of methylphenidate on cognitive performance of healthy male rats

Contact Info

Product

Resources

About