Effects Of Oral Methylphenidate Research Articles

Effect of Oral Methylphenidate on the Experimental Epileptiform Activity in Male Rats

Effect of Oral Methylphenidate on the Experimental Epileptiform Activity in Male Rats

Effects of oral methylphenidate on [18F]fallypride binding in healthy volunteers and adults with attention-deficit hyperactivity disorder (ADHD)

Methylphenidate (MPH) improves performance on tests of prefrontal cognitive functioning in healthy volunteers and adults with ADHD. This study assessed increases of dopamine following a single dose of oral MPH, dopamine D2/D3 receptor availability in adult ADHD patients compared to healthy controls and relationships between dopamine activity, ADHD symptom severity and prefrontal cognitive functioning. 16 adults with ADHD and 16 matched controls were scanned with positron emission tomography (PET) and [18F]fallypride, a high-affinity D2/D3 receptor radiotracer, after a single oral dose of MPH (0.5mg/kg) or placebo in counter-blanaced order. [18F]fallypride binding potentials (BPs) in regions manually defined on magnetic resonance images were calculated using a reference tissue model. Selected CANTAB tasks were administered on both sessions. MPH displaced [18F]fallypride in all striatal sub-regions, globus pallidus and substantia nigra (SN). This effect was similar in patients and controls. Baseline BP in the pre-commissural caudate correlated negatively with attention deficit symptoms and total errors in SWM. BP changes in the SN following MPH correlated positively with baseline performance on RVIP and SWM, and with improved SWM performance following MPH. (All results p<0.01). Our results support a continuum model of dysregulations of the dopamine system and cognitive deficits in ADHD and a specific role of the SN in mediating cognitive enhancing effects of MPH.

Dopamine Release in Dissociable Striatal Subregions Predicts the Different Effects of Oral Methylphenidate on Reversal Learning and Spatial Working Memory

Previous data suggest that methylphenidate can have variable effects on different cognitive tasks both within and between individuals. This is thought to be underpinned by inverted U-shaped relationships between cognitive performance and dopaminergic activity in relatively separate fronto-striatal circuits and reflected by individual differences in trait impulsivity. Direct evidence for this is currently lacking. In this study, we demonstrate for the first time that therapeutic doses of oral methylphenidate administered to young healthy subjects result in different sized changes in D(2)/D(3) receptor availability in different regions of the human striatum and that the change in receptor availability within an individual subregion predicts cognitive performance on a particular task. Methylphenidate produced significantly different effects on reversal learning and spatial working memory tasks within individuals. Performance on the reversal learning task was predicted by the drug-induced change in D(2)/D(3) receptor availability in postcommissural caudate, measured using [(11)C]-raclopride radioligand PET imaging, whereas performance on the spatial working memory task was predicted by changes in receptor availability in the ventral striatum. Reversal learning performance was also predicted by subjects' trait impulsivity, such that the most impulsive individuals benefited more from methylphenidate, consistent with this drug's beneficial effects on cognition in attention deficit hyperactivity disorder.

Reinforcing and subjective effects of methylphenidate in adults with and without attention deficit hyperactivity disorder (ADHD)

There has been controversy over the abuse potential of methylphenidate (MPH) in the context of treatment for attention deficit hyperactivity disorder (ADHD). The objective of this study was to compare the reinforcing and subjective effects of oral MPH in adults with and without ADHD. Following screening, 33 adults (n = 16 with ADHD; n = 17 free from psychiatric diagnoses) completed four pairs of experimental sessions, each of which included a sampling session and a self-administration session. During sampling sessions, subjects received in randomized order 0 (placebo), 20, 40, and 60 mg MPH. During self-administration sessions, subjects completed a progressive ratio (PR) task to earn portions of the dose received on the corresponding sampling session. Subjective effects were recorded throughout all sessions. The main outcome measure for the study was the number of ratios completed on the PR task. Secondary measures included peak subjective effects and area-under-the-curve values for subjective effects. Compared to the control group, the ADHD group completed more ratios on the PR task. Both groups showed robust effects of methylphenidate on subjective endpoints. Main effects of group were noted on subjective effects involving concentration and arousal. Compared to placebo, MPH produced reinforcing effects only for the ADHD group and not for the control group. Increases in stimulant-related subjective effects in non-ADHD subjects were not associated with drug reinforcement.

Effects of oral methylphenidate on prefrontal cortex‐associated neurocognitive deficits in the spontaneous hypertensive rat strain

Though several animal models of Attention Deficit Hyperactivity Disorder (ADHD) exist, the spontaneous hypertensive rat (SHR) model is most frequently used. SHR display the same core behavioral symptoms as individuals with ADHD (hyperactivity, inattention, impulsivity), and also show extradimensional set‐shifting and non‐spatial working memory deficits that are unrelated to hypertension. The objective here was to determine if treatment with methylphenidate could prevent these deficits in the SHR. Extradimensional set‐shifting was assessed using the Attentional Set‐Shift Task and non‐spatial working memory was assessed using the Odor Delayed Win‐Shift Task. The SHR and several comparator rat strains were administered either methylphenidate at a clinically relevant dose (1.5 mg/kg), route (oral) and pretreatment time (30 min), vehicle, or were left untreated. Results demonstrated that treating the SHR with low‐dose oral methylphenidate prevented working memory and set‐shifting deficits that were observed in untreated SHR, and eliminated strain differences in both tasks. The findings provide further evidence that the SHR is a valid model for studying neurocognitive deficits associated with ADHD. Moreover, the current behavioral approach is appropriate to assess novel medications that target neurocognitive deficits associated with ADHD. Supported by SBE‐0354378, RO1 DA11716 and P50 DA05312.

Discriminative Stimulus and Self-Reported Effects of Methylphenidate, d-Amphetamine, and Triazolam in Methylphenidate-Trained Humans.

Asymmetrical generalization between drugs on drug-discrimination procedures has been demonstrated for sedative and stimulant drugs in animals and to some extent with sedative drugs in humans. The aim of this experiment was to examine the discriminative-stimulus effects of d-amphetamine in methylphenidate-trained humans. A previous study demonstrated that methylphenidate substitutes for d-amphetamine in d-amphetamine-trained humans. Six healthy human participants first learned to discriminate 30 mg oral methylphenidate. Doses of oral methylphenidate, d-amphetamine, triazolam, and placebo were then tested to determine whether they share discriminative-stimulus and self-reported effects with 30 mg methylphenidate. Methylphenidate and d-amphetamine dose-dependently increased methylphenidate-appropriate responding and produced prototypical stimulant-like effects. Triazolam produced low levels of methylphenidate-appropriate responding and prototypical sedative-like effects. The results of this experiment are concordant with previous studies and suggest that the behavioral effects of oral methylphenidate and d-amphetamine overlap extensively and that the discriminative-stimulus effects of methylphenidate and d-amphetamine are symmetrical.