Methylphenidate (Ritalin): Behavioral Studies in the Rat

Askenasy, Erik P.; Taber, Katherine H.; Peng, Yang; Dafny, Nachum

doi:10.1080/00207450600910176

Cited by 70 publications

(62 citation statements)

References 136 publications

(407 reference statements)

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“…Although many aspects of the behavioral effects of methylphenidate have been well characterized (for review, see Askenasy et al, 2007), few studies have compared its effects in periadolescent and adult animals. The FA-NA task assesses elementary forms of behavioral plasticity involving learning, memory, arousal level, and attention (Berlyne, 1969;Leussis and Bolivar, 2006), which are highly relevant to ADHD and Fig.…”

Section: Discussionmentioning

confidence: 99%

Differences in Methylphenidate Dose Response between Periadolescent and Adult Rats in the Familiar Arena-Novel Alcove Task

Levant

Zarcone²,

Davis³

et al. 2010

J Pharmacol Exp Ther

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Methylphenidate is a psychostimulant widely used in the treatment of attention deficit hyperactivity disorder. In this study, the effects of two nonstereotypy-inducing doses of methylphenidate (2.5 and 5.0 mg/kg s.c.) were examined in periadolescent [postnatal days (P) 35 and 42] and young adult (P70), male Long-Evans rats using a three-period locomotor activity paradigm that affords inferences about exploration, habituation, and attention to a novel stimulus (an "alcove") in a familiar environment in a single test session. In the first test period, P35 and P42 rats were more active than P70 rats, and methylphenidate increased locomotion in a dose-related manner. The introduction of a novel spatial stimulus in the third test period revealed a significant interaction of dose and age such that P70 rats exhibited dose-related increases in distance traveled, but P35 rats did not. Furthermore, methylphenidate dose-relatedly disrupted the rats' tendency to spend increasing amounts of time in the alcove across the test period at P70 but not at P35. Brain and serum methylphenidate concentrations were significantly lower at P35 than at P70, with intermediate levels at P42. Developmental differences in dopaminergic neurochemistry were also observed, including increased dopamine content in the caudate-putamen, nucleus accumbens, and frontal cortex and decreased densities of D 1 -like receptors in the frontal cortex in P70 than in P42 rats. These results raise the possibility that children and adults may respond differently when treated with this drug, particularly in situations involving response to novelty and that these effects involve developmental differences in pharmacokinetics and dopaminergic neurochemistry.

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Section: Discussionmentioning

confidence: 99%

Differences in Methylphenidate Dose Response between Periadolescent and Adult Rats in the Familiar Arena-Novel Alcove Task

Levant

Zarcone²,

Davis³

et al. 2010

J Pharmacol Exp Ther

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“…Methylphenidate, a dopamine reuptake inhibitor, has been shown to reduce energy intake and especially the intake of fat (23). Furthermore, in animal studies, methylphenidate increased locomotor activity (24,25) and thus might be a helpful compound to overcome physical hypoactivity, which is common in patients with hypothalamic obesity (10,19,26). Orlistat, a gastrointestinal lipase inhibitor, has limited efficacy and can be associated with intolerable side effects that can preclude its use (27,28).…”

Section: Introductionmentioning

confidence: 99%

GLP-1 analogues as a new treatment option for hypothalamic obesity in adults: report of nine cases

Zoicas

Droste

Mayr

et al. 2013

European Journal of Endocrinology

103

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Background: Patients with hypothalamic pathology often develop morbid obesity, causing severe metabolic alterations resulting in increased morbidity and mortality. Glucagon-like peptide-1 (GLP-1) analogues improve glycaemic control in type 2 diabetic patients and cause weight loss in obese patients by yet unknown mechanisms. Here we tested whether GLP-1 analogues were also effective in the treatment of obesity and associated metabolic alterations in patients with hypothalamic disease. Methods: Nine patients (eight with type 2 diabetes mellitus) with moderate to severe hypothalamic obesity were treated with GLP-1 analogues for up to 51 months. Body weight, homeostasis model assessment -insulin resistance (HOMA-IR), HbA1c and lipids were assessed. Results: Eight patients experienced substantial weight loss (K13.1G5.1 kg (range K9 to K22)). Insulin resistance (HOMA-IR K3.2G3.5 (range K9.1 to 0.8)) and HbA1c values (K1.3G1.4% (range K4.5 to 0.0)) improved under treatment (24.3G18.9 months (range 6 to 51)). Five patients reported increased satiation in response to the treatment. Two of the eight patients complained about nausea and vomiting and one of them abandoned therapy because of sustained gastrointestinal discomfort after 6 months. One patient suffered from intolerable nausea and vomiting and discontinued treatment within 2 weeks. Conclusion: GLP-1 analogues can cause substantial and sustained weight loss in obese patients with hypothalamic disease. This offers a new approach for medical treatment of moderate to severe hypothalamic obesity and associated metabolic alterations.

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“…In fact, it has been reported in the past that humans display interindividuality in behavioral responses to psychostimulants (Segal and Kuczenski, 1987;Piazza et al, 1989;Hooks et al, 1991). Thus, although still in its infancy, some investigations have been started considering differential response between rat strains representing the normal population (Wistar rats, Sprague-Dawley rats), from those which mimic the behavioral aberrations seen in ADHD, the SHR (for reviews see Askenasy et al, 2007;Vendruscolo et al, 2009). The advantage of doing experiments in animal models is that we deal with a simpler system and data obtained from these experiments may be easier to interpret to that of the clinical case (Sagvolden and Sergeant, 1998).…”

Section: Discussionmentioning

confidence: 99%

Neuroadaptations Involved in Long-Term Exposure to ADHD Pharmacotherapies: Alterations That Support Dependence Liability of These Medications

Peña¹,

Ahn²,

Shin

et al. 2011

Biomolecules and Therapeutics

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INTRODUCTIONSubstance dependence is one of the most established physiological states following chronic exposure to an addictive drug. It is characterized by a cluster of physio-behavioral and cognitive phenomena which include the persistent desire or unsuccessful efforts to cut down substance abuse, unrestrained drug taking despite harmful consequences, higher priority given to drug use than to other social, recreational activities and obligations, tolerance to the drug's euphorigenic effects and a physical withdrawal state (International Classification of Diseases (ICD)-10).Measuring the dependence liability of a certain substance is a challenging task as some components of dependence cannot be gauged objectively in the laboratory. Pro-addictive behaviors such as tolerance and withdrawal can be well studied in animal subjects and they have provided us with important information on the effects of drugs on health and longterm consequences of substance use. However, it is diffi cult to measure the cognitive aspect of dependence (such as drug craving, loss of control and persistent drug use), although this is slowly being addressed by recent neuroimaging techniques Repeated administration of addictive drugs causes cellular and molecular changes believed to be the mechanism of pro-addictive behaviors. Neuroadaptations also take place with repeated administration of amphetamine, methylphenidate and atomoxetine, drugs for Attention Defi cit Hyperactivity Disorders (ADHD), and it is speculated that these changes may serve as markers to demonstrate the dependence liability of these therapies. In this review, we enumerate the neuroadaptive changes in molecules associated with neuronal signaling and plasticity, as well as neuronal morphology wrought by repeated administration of ADHD medications. We provide the current perspective on the dependence liability of these therapies, and also suggest of some factors that need to be considered in future investigations, so that what is drawn from animal studies would be better consolidated with those known clinically. (Maganti, 2004). On the other hand, a number of studies have emerged and those investigations center on the molecular and cellular changes in the brain associated with chronic

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Methylphenidate (Ritalin): Behavioral Studies in the Rat

Cited by 70 publications

References 136 publications

Differences in Methylphenidate Dose Response between Periadolescent and Adult Rats in the Familiar Arena-Novel Alcove Task

Differences in Methylphenidate Dose Response between Periadolescent and Adult Rats in the Familiar Arena-Novel Alcove Task

GLP-1 analogues as a new treatment option for hypothalamic obesity in adults: report of nine cases

Neuroadaptations Involved in Long-Term Exposure to ADHD Pharmacotherapies: Alterations That Support Dependence Liability of These Medications

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