Characterization of methylphenidate self-administration and reinstatement in the rat

Botly, Leigh C.P.; Burton, Christie L.; Rizos, Zoë; Fletcher, Paul

doi:10.1007/s00213-008-1093-z

Cited by 38 publications

(57 citation statements)

References 83 publications

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“…Methylphenidate self-administration on a PR schedule After completion of methylphenidate self-administration tests under the FR schedule, rats were trained to respond for methylphenidate under the progressive ratio (PR) schedule. The methods employed were the same as those outlined by Botly et al (2008), with some modifications. The methylphenidate dose used to train the rats in this schedule was 0.125 mg per infusion.…”

Section: Methodsmentioning

confidence: 99%

“…Over this period, rats acquired active self-administration based on significantly higher rate of lever response for the active than the inactive lever (95% confidence limit). During these sessions, both levers (active and inactive [non-reinforced]) were present, and a response on the active lever resulted to the delivery of 0.1 ml methylphenidate (0.25 mg) (Botly et al 2008) and the illumination of the stimulus light above it. The light was lit for 10 s and remained illuminated for 20 s after the end of the infusion.…”

Section: Methodsmentioning

confidence: 99%

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Methylphenidate treatment in the spontaneously hypertensive rat: influence on methylphenidate self-administration and reinstatement in comparison with Wistar rats

et al. 2011

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The contrasting effects of repeated methylphenidate treatment in methylphenidate self-administration and reinstatement in Wistar and SHR, and the increased susceptibility of the Wistar rat strain to the reinforcing effects of methylphenidate indicate that "normal" individuals are more likely to develop psychological dependence to the drug and experience relapse. Meanwhile, the clinical use of methylphenidate may not produce drug dependence or relapse in ADHD patients.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Methylphenidate treatment in the spontaneously hypertensive rat: influence on methylphenidate self-administration and reinstatement in comparison with Wistar rats

et al. 2011

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“…The dose for the SCH-23390 was chosen based on previous work by Meririnne et al [12], which showed that these doses were sufficient to alleviate MPH-induced CPP in adult male rats. The doses for eticlopride HCl were based on past work by Botly et al [33], which demonstrated that these doses were sufficient to increase the number of infusions taken by rats trained to self-administer MPH. A two-way ANOVA was used as the primary statistic and Dunnett's multiple comparison test (p = 0.05) was used for all post hoc analyses.…”

Section: Methodsmentioning

confidence: 99%

The Role of Dopamine D<sub>1</sub> and D<sub>2</sub> Receptors in Adolescent Methylphenidate Conditioned Place Preference: Sex Differences and Brain-Derived Neurotrophic Factor

Cummins

Griffin²,

Duty³

et al. 2014

Dev Neurosci

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This study analyzed the role of dopamine D₁ and D₂ receptors in methylphenidate (MPH) conditioned place preference (CPP) in adolescent male and female rats, in addition to the role of these receptors in the effects of MPH on brain-derived neurotrophic factor (BDNF) in the dorsal striatum and nucleus accumbens. Using a nonbiased CPP procedure, the animals were conditioned from postnatal day (PD) 33 to 37. On conditioning trials, animals were first administered saline or their respective antagonist (0.1 or 0.2 mg/kg SCH-23390; 0.01 or 0.03 mg/kg eticlopride HCl), followed by MPH (5 mg/kg). Approximately 10 min after MPH administration, the rats were placed into the paired context for a 10-min trial. One day after conditioning on PD38, a preference test was administered with dividers removed. One day following the preference test on PD39, brain tissue was removed, and the nucleus accumbens and striatum were analyzed for BDNF. Results revealed that MPH conditioning resulted in an increased preference that was blocked by either dose of SCH-23390, but generally not affected by either dose of eticlopride. Further, the higher dose of SCH-23390 resulted in a conditioned place aversion in males, presumably due to an increased number of dopamine D₁ receptors in adolescent males. MPH produced a significant increase of striatal and accumbal BDNF alleviated by SCH-23390 or eticlopride. These results show that MPH results in CPP in adolescent male and female rats and these effects appear to be mediated by the dopamine D₁ receptor, but the effects of MPH on BDNF appear to be mediated by both dopamine receptor families.

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“…Notwithstanding this trend, there is concern that the rise in therapeutic use of MPH might coincide with a rise in its nontherapeutic, nonmedical (mis)use. Intranasal MPH produces a euphoric sensation or "high" in humans (Volkow and Swanson 2003), and rats readily self-administer this drug intravenously (Collins et al 1984;Fletcher et al 2007;Botly et al 2008). College students and adolescents might be attracted to MPH for its attention-focusing, weight-loss, or euphoric effects.…”

Section: Adhd and The Use Of Mphmentioning

confidence: 98%

Brain Processes in Discounting: Consequences of Adolescent Methylphenidate Exposure

Adriani

Zoratto

Laviola

2011

Behavioral Neuroscience of Attention Deficit Hyperactivity Disorder and Its Treatment

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Traits of inattention, impulsivity, and motor hyperactivity characterize children diagnosed with attention-deficit/hyperactivity disorder (ADHD), whose inhibitory control is reduced. In animal models, crucial developmental phases or experimental transgenic conditions account for peculiarities, such as sensation-seeking and risk-taking behaviors, and reproduce the beneficial effects of psychostimulants. An "impulsive" behavioral profile appears to emerge more extremely in rats when forebrain dopamine (DA) systems undergo remodeling, as in adolescence, or with experimental manipulation tapping onto the dopamine transporter (DAT). Ritalin(®) (methylphenidate, MPH), a DAT-blocking drug, is prescribed for ADHD therapy but is also widely abused by human adolescents. Administration of MPH during rats' adolescence causes a long-term modulation of their self-control, in terms of reduced intolerance to delay and diminished proneness for risk when reward is uncertain. Exactly the opposite profile emerges when exogenous alteration of DAT levels is achieved via lentiviral transfection. Both adolescent MPH exposure and DAT-targeting transfection lead to enduring hyperfunction of dorsal striatum and hypofunction of ventral striatum. Together with upregulation of prefronto-cortical phospho-creatine, striatal upregulation of selected genes (like serotonin 7 receptor gene) suggests that enhanced inhibitory control is generated by adolescent MPH exposure. Operant tasks, which assess the balance between motivational drives and inhibitory self-control, are thus useful for investigating reward-discounting processes and their modulation by DAT-targeting tools. In summary, due to the complexity of human studies, preclinical investigations of rodent models are necessary to understand better both the neurobiology of ADHD-like symptoms' etiology and the long-term therapeutic safety of adolescent MPH exposure.

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Characterization of methylphenidate self-administration and reinstatement in the rat

Cited by 38 publications

References 83 publications

Methylphenidate treatment in the spontaneously hypertensive rat: influence on methylphenidate self-administration and reinstatement in comparison with Wistar rats

Methylphenidate treatment in the spontaneously hypertensive rat: influence on methylphenidate self-administration and reinstatement in comparison with Wistar rats

The Role of Dopamine D<sub>1</sub> and D<sub>2</sub> Receptors in Adolescent Methylphenidate Conditioned Place Preference: Sex Differences and Brain-Derived Neurotrophic Factor

Brain Processes in Discounting: Consequences of Adolescent Methylphenidate Exposure

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