Repeated exposure of adolescent rats to oral methylphenidate does not induce behavioral sensitization or cross-sensitization to nicotine

Justo, C.C.; Carneiro-de-Oliveira, P.E.; DeLucia, Roberto; Aizenstein, Moacyr Luiz; Planeta, Cleópatra da Silva

doi:10.1590/s0100-879x2010007500042

Cited by 9 publications

(10 citation statements)

References 35 publications

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“…Another study designed to evaluate the cardiovascular impact of a less prolonged exposure (3 weeks) of mice to pollution showed no differences in the studied variables (blood pressure, heart rate, heart rate variability and baroreflex response to nitroprusside stimulus) between the exposed and non-exposed group 52 . Justo et al 53 evaluated in young rats, whether the use of stimulant drugs such as methylphenidate (MPH), could facilitate the nicotine addiction, as suggested by some studies in humans. However, the study did not show cross-sensitization, suggesting that the MPH treatment did not induce neuroadaptation in rats that could increase sensitivity to nicotine.…”

Section: Experimental Studiesmentioning

confidence: 99%

Tabagismo: o que tem sido abordado em periódicos brasileiros

Prado¹,

Lombardi²,

Miethke-Morais³

et al. 2012

Arq. Bras. Cardiol.

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Section: Experimental Studiesmentioning

confidence: 99%

Tabagismo: o que tem sido abordado em periódicos brasileiros

Prado¹,

Lombardi²,

Miethke-Morais³

et al. 2012

Arq. Bras. Cardiol.

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“…Several of these studies injected MP either subcutaneously or intraperitoneally, which differs significantly from oral administration, specifically with respect to time to peak serum concentration, half-life, and rate of elimination (Kuczenski and Segal, 2001), as well as absolute magnitude and time course of increases in extracellular DA and locomotor responses (Gerasimov et al, 2000; Kuczenski and Segal, 2001). Studies that have used oral dosing have done so by gavage (Kuczenski and Segal, 2001; Justo et al, 2010), which is stressful and can cause injury (Brown et al, 2000; Balcombe et al, 2004), or by administering MP on an oyster cracker or by mixing with chow (LeBlanc-Duchin and Taukulis, 2007; Zhu et al, 2010). Although the latter is less stressful and dangerous, oral administration results in peak serum concentration 15 min post-administration, and this concentration has been shown to drop by half within an additional 5 min (Patrick et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

Sex Differences in the Physiological and Behavioral Effects of Chronic Oral Methylphenidate Treatment in Rats

Robison

Michaelos

Gandhi

et al. 2017

Front. Behav. Neurosci.

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Methylphenidate (MP) is a psychostimulant prescribed for Attention Deficit Hyperactivity Disorder. Previously, we developed a dual bottle 8-h-limited-access-drinking-paradigm for oral MP treatment of rats that mimics the pharmacokinetic profile of treated patients. This study assessed sex differences in response to this treatment. Male and female Sprague Dawley rats were assigned to one of three treatment groups at 4 weeks of age (n = 12/group): Control (water), low dose (LD) MP, and high dose (HD) MP. Rats drank 4 mg/kg MP (LD) or 30 mg/kg MP (HD) during the first hour, and 10 mg/kg (LD) or 60 mg/kg MP (HD) for the remaining 7 h each day. Throughout 3 months of treatment, rats were monitored for body weight, food intake, and fluid intake; as well as tested for open field behavior, circadian activity, novel object recognition, and social interaction. Chronic MP treated rats exhibited reduced fluid intake during distinct treatment weeks to a greater extent in males, and reduced total fluid intake in males only. HD MP treatment decreased body weight in both sexes, while HD MP increased total food intake in females only, likely to offset energy deficits resulting from MP-induced hyperactivity. LD and HD MP increased locomotor activity in the open field, particularly in females and during later treatment weeks. MP dose-dependently increased activity during the dark cycle of circadian testing in females, while in males hyperactivity was only exhibited by HD rats. HD MP increased center activity to a greater extent in males, while MP increased rearing behavior in females only. MP had no effect on social behavior or novel object recognition in either sex. This study concludes that chronic oral MP treatment at clinically-relevant dosages has significant effects on food intake, body weight, open field behavior, and wake cycle activity. Particularly marked sex differences were apparent for locomotor activity, with females being significantly more sensitive to the hyperactivating effects of the drug. These findings suggest that chronic MP exposure beginning in adolescence can have significant behavioral effects that are both dose- and sex-dependent, and raise concerns regarding the reversibility of these effects post-discontinuation of treatment.

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“…Additionally, many studies that have aimed to explore the effects of oral MP utilize the gavage method (Kuczenski and Segal, 2002; Justo et al, 2010), which can result in a significant stress response, as well as aspiration, and/or pulmonary injury in rats (Brown et al, 2000; Balcombe et al, 2004). Other studies have utilized voluntary oral consumption of MP (administered on oyster crackers or mixed with chow) to avoid these issues (LeBlanc-Duchin and Taukulis, 2007; Zhu et al, 2010); however, these methods also have some limitations.…”

Section: Introductionmentioning

confidence: 99%

A pharmacokinetic model of oral methylphenidate in the rat and effects on behavior

Thanos

Robison

Steier

et al. 2015

Pharmacology Biochemistry and Behavior

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Most animal studies using methylphenidate (MP) do not administer it the same way it is administered clinically (orally), but rather by injection, resulting in an altered pharmacokinetic profile (i.e. quicker and higher peak concentrations). Here, we evaluated several oral-dosing regimens in rats, including dual-dose drinking, to mimic the clinical drug delivery profile. Using an 8-hour-limited-access-drinking-paradigm, MP solutions were delivered at different doses (20, 30, or 60 mg/kg/day; as well as dual-dosages of 4 and 10 mg/kg/day, 20 and 30 mg/kg/day, or 30 and 60 mg/kg/day, in which the low dose was administered in the first hour of drinking followed by 7 h of drinking the high dose). Blood was sampled and plasma was assayed for MP levels at many time points. Results showed that an 8-hour limited drinking of a dual-dosage 30/60 mg/kg MP solution achieved a pharmacokinetic profile similar to clinically administered doses of MP at the high end of the spectrum (peaking at ~30 ng/mL), while the 4/10 mg/kg MP dual-dosage produced plasma levels in the range produced by typically prescribed clinical doses of MP (peaking at ~8 ng/mL). Treatment with the higher dual-dosage (HD: 30/60 mg/kg) resulted in hyperactivity, while the lower (LD: 4/10 mg/kg) had no effect. Next, chronic effects of these dual-dosages were assessed on behavior throughout three months of treatment and one month of abstinence, beginning in adolescence. MP dose-dependently decreased body weight, which remained attenuated throughout abstinence. MP decreased food intake during early treatment, suggesting that MP may be an appetite suppressant and may also speed metabolism and/or suppress growth. Chronic HD MP resulted in hyperactivity limited during the dark cycle; decreased exploratory behavior; and increased anxiolytic behavior. These findings suggest that this dual-dosage-drinking-paradigm can be used to examine the effects of clinically relevant pharmacokinetic doses of MP, and that chronic treatment with such dosages can result in long-lasting developmental and behavioral changes.

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Repeated exposure of adolescent rats to oral methylphenidate does not induce behavioral sensitization or cross-sensitization to nicotine

Cited by 9 publications

References 35 publications

Tabagismo: o que tem sido abordado em periódicos brasileiros

Tabagismo: o que tem sido abordado em periódicos brasileiros

Sex Differences in the Physiological and Behavioral Effects of Chronic Oral Methylphenidate Treatment in Rats

A pharmacokinetic model of oral methylphenidate in the rat and effects on behavior

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