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Recent investigations have suggested an additional and more immediate component to corticosteroid action mediated by an interaction with membrane-bound protein receptors, namely the α7-nicotinic acetylcholine receptor (CAMRA); the N-methyl-D-aspartate (NMDA)-receptor (NMDA); nicotinic-substituted G protein-coupled receptors; and the dopamine D3 receptor (D3R). An earlier study involving the treatment of mice with different compounds that interact with these receptor subtypes found that the AMPA receptor was the most effective, followed by the NMDA and D3Rs. The relationship between the specific neurotransmitter involved and the treatment is critical in determining the optimal therapeutic dose. Thus, it is likely the modulation of these receptors by a single agent would result in a therapeutic outcome that is dependent on an optimal balance of these specific receptors.

Thus, the most important question in therapy at present is whether the optimal combination of all currently available agents and therapeutic levels is feasible. A variety of preclinical studies have demonstrated that certain agents have the potential to treat ADHD. Many of these studies have investigated combinations of agents that improve performance on tasks of attention and sustained attention in a variety of laboratory and rat models of ADHD. In a number of these studies individuals receiving individual agents developed the following problems. Specifically, these individuals had difficulty in establishing and maintaining sustained attention in addition to other problems associated with ADHD, including impaired motor skills.

The majority of these researchers believe that the only treatment method effective for treatment of ADHD is through an individual combination based on individual genetics. However, studies are ongoing to further understand the relationship between genetics and the development of ADHD and this has yielded some interesting results. There is a clear genetic relationship between children born within 5 days of each other that indicates an individual’s risk for the development of ADHD. However, many of these same genes are located in nonhuman primates, most notably in the primate brain, indicating that the same genes involved in their development may also play a role in the development of ADHD. In addition, these gene variants affect the risk for ADHD. Other factors including environmental factors and other genes may also play roles in the development of ADHD.

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