Acute and chronic methylphenidate dose–response assessment on three adolescent male rat strains

Peng, Yang; Swann, Alan C.; Dafny, Nachum

doi:10.1016/j.brainresbull.2006.09.019

Cited by 91 publications

(80 citation statements)

References 66 publications

(82 reference statements)

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“…Additionally, there is no sex difference in hyperactivity in the SHR strain (Berger and Sagvolden 1998). Moreover, SHR show hyperactivity when compared to WKY rats but they are not more active than other outbred rat strains such as Wistar and SpragueDawley rats (Ferguson and Cada 2003;Yang et al 2006;Hård et al 1985;Goto et al 1993;Ernsberger et al 1983;Paré 1989;Sagvolden et al 1993).…”

Section: Introductionmentioning

confidence: 91%

Comparison of SHR, WKY and Wistar rats in different behavioural animal models: effect of dopamine D1 and alpha2 agonists

Langen

Dost

2010

ADHD Atten Def Hyp Disord

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Spontaneously hypertensive rats (SHR) and its counterpart, the Wistar-Kyoto rats (WKY), are probably the most often used animal model of ADHD. However, SHR as model of ADHD have also been criticised partly because of not differing to outbred rat strains. In the present study, adolescent SHR, WKY and Wistar rats from Charles River were tested in open-field, elevated plus maze and novel object recognition and on gastrointestinal transport to more intensively evaluate the strain characteristics. Non-habituated SHR and Wistar rats were more active than WKY rats but contrary to Wistar rats SHR stay hyperactive in a familiar environment. SHR were more sensitive to the alpha2-adrenoceptor agonist guanfacine and the dopamine D1 agonist A-68930 than WKY and Wistar rats, whereas amphetamine, the D1/D5 agonist ABT431 and the D2 agonist quinpirole, similarly affected open-field activity in all strains. In the elevated plus maze, SHR and Wistar rats showed less anxiety-related behaviour than WKY rats. Guanfacine and amphetamine induced an anxiolytic-like activity in SHR but not in WKY and Wistar rats. SHR showed the highest long-term memory in the novel object recognition. Gastrointestinal transport was similar and comparably affected by guanfacine in all rat strains. The present study shows clear differences in the behaviour of SHR and Wistar rats but also of WKY and Wistar rats. The use of SHR as animal model of ADHD is supported.

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Section: Introductionmentioning

confidence: 91%

Comparison of SHR, WKY and Wistar rats in different behavioural animal models: effect of dopamine D1 and alpha2 agonists

Langen

Dost

2010

ADHD Atten Def Hyp Disord

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“…It has also been reported that there are strain differences in the effects of MPH administered to juvenile rats (Yang et al, 2006). Male spontaneously hyperactive/hypertensive rats, Wistar-Kyoto rats, and Sprague-Dawley rats, 34-41 days old, were administered MPH via intraperitoneal injections on a single day or for 11 days at doses of 0.6, 2.5, or 10.0 mg/kg.…”

Section: Introductionmentioning

confidence: 99%

Juvenile toxicity assessment of d,l‐methylphenidate in rats

Beckman¹,

Schneider²,

Youreneff³

et al. 2008

Birth Defects Research Pt B

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BACKGROUND:The oral administration of d,l-methylphenidate (MPH) was designed to encompass the major part of postnatal development in the rat and to evaluate potential chronic effects. METHODS: Wistar Hannover rats were crossfostered on postpartum day 0 (day of birth) and were administered MPH at doses of 5, 50, and 100 mg/kg/day (mpkd) on postpartum days 7 to 70. Clinical signs, body weight, food consumption, developmental, behavioral, clinical/ anatomic pathology, toxicokinetic, and fertility evaluations were conducted. RESULTS: MPH-related effects on clinical signs, body weight, and behavior tests were noted. Increased locomotor activity and cage biting/chewing occurred at Z 5 mpkd (females) and Z 50 mpkd (males) and were absent after dosing ceased. Body weight parameters were decreased at Z 50 mpkd and were comparable to controls at 5 weeks' recovery. Open field motor activity tests conducted 2 weeks after dosing ceased revealed decreased peripheral beam breaks at Z 50 mpkd. Passive avoidance tests conducted 3 weeks after dosing ceased indicated decreased females reaching learning criterion at 100 mpkd. This is considered of nominal significance as there were no effects in the water maze test or retention in passive avoidance test. After multiple doses, females exhibited higher exposures than males and exposures were reduced in all groups in comparison to those after a single dose. CONCLUSIONS: These results suggest that MPH can produce enduring behavioral effects in rats. The no-toxicologic-effect-level was 5 mpkd, associated with AUC (0-24 h) racemate values in males and females, respectively, of 101 and 153 ng.h/mL after chronic dosing. Birth Defects Res (Part B) 83: 48-67, 2008.

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“…Previous studies [15]- [20] [25]- [27] using identical protocol reported minor, insignificant fluctuations in the behavioral and electrophysiological study of rats injected with saline vs. rats that received no injection. The above studies have shown that time (42 days) and repetitive saline injections (42 days) exhibit similar activity with minor and insignificant fluctuations [15] [16] [19]. This permits the use of saline injection at ED 1 as a control for the drug effect (injections (0.8 ml) and handling of the animals.…”

Section: Discussionmentioning

confidence: 99%

“…), are calculated as freebase. Dosages were selected from prior MPD dose response studies [6] [14]- [19] [21]. These studies assessed the dose responses of eight different concentrations of MPD, in which three were selected.…”

Section: Drugsmentioning

confidence: 99%

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Ritalin Use Modifies Alcohol Effects in Rats

Sonne¹,

Dafny²

2014

JBBS

Self Cite

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Methylphenidate (MPD), known as Ritalin, is a common drug prescribed for those diagnosed with Attention Deficit Hyperactivity Disorder (ADHD).There are reports that many MPD users consume alcohol, resulting in toxic effects and hospitalization. The goal of this study was to investigate the effects of ethanol in rats concomitant with acute and repetitive MPD exposure. Rats were divided into four groups, control (saline), 0.6 mg/kg MPD, 2.5 mg/kg MPD, and 10.0 mg/kg MPD groups and lasted for 12 consecutive days. Ethanol was given after repeated MPD administration as follows. On experimental day 1 (ED 1), all animals were treated with saline to establish baseline, on ED 2 through ED 7 either saline or MPD (0.6, 2.5, or 10.0 mg/kg) was given. On ED 11, after three days without treatment (ED 8 -10), rats were treated as they were on ED 2 -7. At ED 12, 1 g/kg ethanol was administered, and one hour of locomotor activity was recorded after alcohol administration, using the open field assay. The data show a dose response characteristic of increased locomotor activity with increasing doses of MPD. Ethanol administration alone depresses locomotor activity. The depressive effect of alcohol was significantly attenuated in animals treated with MPD, in a dose dependent manner. The higher dose of MPD previously administered resulted in a larger attenuation of the ethanol's suppressive effect. These trends demonstrate that chronic MPD exposure directly influences the effects of alcohol in rats. Under these circumstances, it is reasonable to assume that a subject will need to consume an increased amount of ethanol in order to attain the ethanol effect desired. This discrepancy between effects and exposure may be a liability for ethanol toxicity.

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Acute and chronic methylphenidate dose–response assessment on three adolescent male rat strains

Cited by 91 publications

References 66 publications

Comparison of SHR, WKY and Wistar rats in different behavioural animal models: effect of dopamine D1 and alpha2 agonists

Comparison of SHR, WKY and Wistar rats in different behavioural animal models: effect of dopamine D1 and alpha2 agonists

Juvenile toxicity assessment of d,l‐methylphenidate in rats

Ritalin Use Modifies Alcohol Effects in Rats

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