Amphetamine Mechanisms and Actions at the Dopamine Terminal Revisited

Neuroscience Program and Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 05/2013; 33(21):8923-8925. DOI: 10.1523/JNEUROSCI.1033-13.2013
Source: PubMed
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    • "Amphetamines are potent sympathomimetic drugs, increasing synaptic levels of dopamine, norepinephrine, and serotonin within the synapse through multiple mechanisms [29, 30]. Although amphetamines bind to all monoamine transporters, its behavioral stimulant effects are mediated primarily through dopamine. "
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    ABSTRACT: Objective: Determining the etiology of unexplained leukocytosis in asymptomatic patients may incur unnecessary testing, cost, and prolonged emergency department stay. The objective was to delineate if use of amphetamines and/or cocaine is a factor. Methods: For two years we reviewed all psychiatric patients presenting for medical clearance with exclusions for infection, epilepsy, trauma, or other nonpsychiatric medical conditions. Results: With a total of 1,206 patients, 877 (72.7%) amphetamines/cocaine-negative drug screen controls had mean WBC 8.4 ± 2.6 × 10³/µL. The 240 (19.9%) amphetamines-positive, cocaine-negative, patients had WBC 9.4 ± 3.3 × 10³/µL (P < 0.0001). The 72 (6.0%) amphetamines-negative, cocaine-positive, patients had WBC 7.1 ± 1.8 × 10³/µL (P < 0.0001). The remaining 17 (1.4%) amphetamines/cocaine-positive patients had WBC 10.0 ± 4.2 × 10³/µL (P = 0.01). Amphetamines-positive patients had a supranormal WBC ratio significantly higher than controls (23.8% versus 14.8%, P = 0.001), whereas only one cocaine-positive patient had a supranormal WBC count, with significantly lower ratio (1.4%, P = 0.0003). Conclusion: Use of amphetamines, not cocaine, may be associated with idiopathic leukocytosis. This may be explained by unique pharmacologic, neuroendocrine, and immunomodulatory differences.
    The Scientific World Journal 01/2014; 2014:207651. DOI:10.1155/2014/207651 · 1.73 Impact Factor
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    ABSTRACT: Methylphenidate (MPH) is commonly diverted for recreational use, but the neurobiological consequences of exposure to MPH at high, abused doses are not well defined. Here we show that MPH self-administration in rats increases dopamine transporter (DAT) levels and enhances the potency of MPH and amphetamine on dopamine responses and drug-seeking behaviours, without altering cocaine effects. Genetic overexpression of the DAT in mice mimics these effects, confirming that MPH self-administration-induced increases in DAT levels are sufficient to induce the changes. Further, this work outlines a basic mechanism by which increases in DAT levels, regardless of how they occur, are capable of increasing the rewarding and reinforcing effects of select psychostimulant drugs, and suggests that individuals with elevated DAT levels, such as ADHD sufferers, may be more susceptible to the addictive effects of amphetamine-like drugs.
    Nature Communications 11/2013; 4:2720. DOI:10.1038/ncomms3720 · 11.47 Impact Factor
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    ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) is a neurobiological condition of childhood onset with the hallmarks of inattention, impulsivity, and hyperactivity. Inattention includes excessive daydreaming, disorganization, and being easily distracted. Impulsivity manifests as taking an action before fully thinking of the consequences. Hyperactivity includes an excessive rate of speech and motor activity. Complications of ADHD include academic failure, low self-esteem, poor work performance, substance abuse, criminal justice issues, and social problems. ADHD is predominately due to decreased activity in the frontal lobe. Dopamine and norepinephrine are the main neurotransmitters involved in the pathophysiology of ADHD. Pharmacological treatment of ADHD includes psychostimulants, norepinephrine reuptake inhibitors, α2 agonists, bupropion, and monoamine oxidase inhibitors. The most effective medications are the psychostimulants. Nonpharmacological treatment of ADHD includes coaching, providing structure, academic accommodations, and work accommodations.
    Journal of Pharmacy Practice 08/2014; 27(4):336-349. DOI:10.1177/0897190014543628
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