**Part 2**

**Psychopharmacology: Mechanisms and Effects** 

88 Current Directions in ADHD and Its Treatment

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**5** 

*USA* 

**The Neuropsychopharmacology** 

Paul E.A. Glaser and Greg A. Gerhardt

*University of Kentucky* 

**of Stimulants: Dopamine and ADHD** 

In this chapter we consider the neuropsychopharmacology of ADHD in general and dopamine and the stimulants more specifically. Attention will be given to the various neurotransmitter theories for ADHD. We will consider the theoretical mechanisms of actions for the various medicines used to treat ADHD. We will look at how the stimulants, although often assumed to be similar, actually show evidence of differential mechanisms of action. We will look at new data that utilizes the technique of reverse microdialysis to demonstrate how different the dose-response curves are for dopamine release in the

Throughout the text we will use ADHD (Attention-Deficit/Hyperactivity Disorder) without reference to the DSM-IV type, unless a specific reference pertains to combined, inattentive or

The stimulant medications were discovered serendipitously with the indirect observation that amphetamines calmed and focused children who were given the medicine to try to treat headache that was caused by the technique of pneumoencephalography, a largely outdated procedure where the spinal fluid was drained and replaced with air in order to see the brain more clearly on X-ray (Bradley, 1937, Strohl, 2011). The form of amphetamine used by Bradley was Benzedrine, the racemic mixture, or 50/50 mixture of d- and l-amphetamine. Because of research pointing to the dopamine releasing qualities of the stimulants, the earliest theory for ADHD was that it represented a hypodopaminergic state. This hypodopaminergic state theoretically led to alterations in reward sensitivity if it was in the nucleus accumbens, hyperactivity if lowered dopamine was in the striatum, and decreased inhibitory control if the lowered dopamine was in the frontal cortex. Although the collective data never supported such clean demarcations in brain structure and dependence solely on dopamine, the

"hypodopaminergic" theory of ADHD is still a popular teaching in the clinical setting.

Dopamine was not always considered a neurotransmitter. As details about the neurotransmitters were emerging dopamine was noted as the penultimate molecule in the

striatum following local application of the different stimulants.

**2. Neuropsychopharmacology of stimulants** 

**1. Introduction**

hyperactive subtypes.

**2.1 Dopamine and ADHD** 
