27 Regarding normal healthy individuals, other authors were able to show evidence of a similar reduction in DAT under methylphenidate in a PET investigation with [C-ll] cocaine.28 In conclusion, the SPECT investigations on DAT confirmed the supposition that with ADHD an impairment is present mainly in the dopaminergic system. This can be improved with the introduction of stimulants. Our initial results show Inhibitors,research,lifescience,medical that, nonresponders to methylphenidate do not reveal raised DAT in striatum prior to therapy, whereas the responders seem to have a high DAT availability (Figure 4).29 Figure 2. DAT availability in striatum, measured with

TRODAT-1 SPECT, in 17 adults with ADHD before and after (in 16 patients) 4 weeks of intake of 5 mg methylphenidate

3 times daily, compared with 16 controls, and in relation to age. DAT, dopamine NVP-TAE684 concentration transporter; … Figure 3. DAT availability in the striatum Inhibitors,research,lifescience,medical of smoking and nonsmoking adults with ADHD with only inattentive symptoms since childhood and with hyperactivity/impulsivity in the childhood, mostly in combination with attention deficit and in nonsmoking controls, shown … Figure 4. Specific binding of striatal DAT, measured with [99mTc]TRODAT-1 SPECT in 1 8 adults with ADHD (percentage of deviation Inhibitors,research,lifescience,medical from values of controls of the same age) in relation to CGI values after 10 weeks of intake of methylphenidate. DAT, dopamine transporter; …

It should be noted, for possible diagnostic applications of SPECT, that the DAT concentration decreases with increase of age30 and that nicotine may influence DAT availability.12 The lowering of DAT with increasing age may be Inhibitors,research,lifescience,medical an explanation for our observation, that most, adults need lower doses of methylphenidate compared with children and adolescents. Nicotine seems to have a similar effect on the DAT as do stimulants (Figure 3). Investigating potential reasons for the lower elevation in Inhibitors,research,lifescience,medical the TRODAT-1 study compared with the altropane study, we found a subgroup of patients with relatively little increase in DAT despite severe clinical impairments; further questioning of these patients revealed that all of them were cigarette smokers. Comparison of 11 smoking nonmedicated patients with ADHD with sex- and agematched nonsmoking drug-naive adults with ADHD showed significantly PDK4 higher DAT density in the nonsmoking patients, despite higher ADHD scores for the smokers.31 This finding suggests that nicotine may act, directly on DAT in the same manner as stimulants. In a self-trial, DAT availability was reduced by over 50% 5 hours after intake of 20 mg methylphenidate in a slow-release formulation; wearing a nicotine skin patch, equaling 10 to 20 cigarettes daily, for 5 hours.