The association between level of dopamine D2 receptors and metabolism in the orbit ofrontal cortex in methamphetamine abusers suggests that D2 receptor-mediated dysregulation of the orbitofrontal cortex could underlie a common mechanism for loss of control and compulsive drug intake in drug-addicted subjects.
It is suggested that protracted abstinence may reverse some of methamphetamine-induced alterations in brain DA terminals, and neuropsychological tests did not improve to the same extent as during short abstinence, which suggests that the increase of the DA transporters was not sufficient for complete function recovery.
Evidence is provided that methamphetamine at dose levels taken by human abusers of the drug leads to dopamine transporter reduction that is associated with motor and cognitive impairment and the urgency of alerting clinicians and the public of the long-term changes that methamphetamine can induce in the human brain.
There is direct evidence that oral methylphenidate at doses within the therapeutic range significantly increases extracellular DA in human brain, and this result coupled with recent findings of increased dopamine transporters in ADHD patients provides a mechanistic framework for the therapeutic efficacy of methyl phenidate.
Evidence is provided that, in humans, methamphetamine abuse results in changes in function of dopamine- and nondopamine-innervated brain regions, and the higher metabolism seen in the parietal cortex is the result of methamphetamine effects in circuits other than those modulated by dopamine.
The results indicate that for a given dose of methylphenidate, individual differences in DAT blockade are not the main source for the intersubject variability in MP‐induced increases in DA, which suggests that for an equivalent level of D AT blockade, MP would induce smaller DA changes in subjects with low than with high DA cell activity.
The results provide the first evidence that dopamine in the dorsal striatum is involved in food motivation in humans that is distinct from its role in regulating reward through the NA, and the ability of methylphenidate to amplify weak dopamine signals is demonstrated.
Assessment of the levels of occupancy of DA D2 receptors by dopamine achieved by doses of cocaine or methylphenidate found them to be consistent with the slower striatal clearance kinetics of [ 11C]methylphenidate than [11C]cocaine observed in previous PET experiments and with the approximately twofold higher potency of methyl phenidate than cocaine in in vitro experiments.