These findings suggest that longer use of methamphetamine may cause more severe psychiatric symptoms and greater reduction of dopamine transporter density in the brain. They also show that the dopamine transporter reduction may be long-lasting, even if methamphetamine use ceases. Further, persistent psychiatric symptoms in methamphetamine users, including psychotic symptoms, may be attributable to the reduction of dopamine transporter density.

BackgroundVarious lines of evidence have shown that bisphenol A [BPA; HO-C6H4-C(CH3)2-C6H4-OH] acts as an endocrine disruptor when present in very low doses. We have recently demonstrated that BPA binds strongly to human estrogen-related receptor-γ (ERR-γ ) in a binding assay using [3H]4-hydroxytamoxifen ([3H]4-OHT). We also demonstrated that BPA inhibits the deactivation activity of 4-OHT.ObjectivesIn the present study, we intended to obtain direct evidence that BPA interacts with ERR-γ as a strong binder, and also to clarify the structural requirements of BPA for its binding to ERR-γ.MethodsWe examined [3H]BPA in the saturation binding assay using the ligand binding domain of ERR-γ and analyzed the result using Scatchard plot analysis. A number of BPA derivatives were tested in the competitive binding assay using [3H]BPA as a tracer and in the luciferase reporter gene assay.Results[3H]BPA showed a KD of 5.50 nM at a Bmax of 14.4 nmol/mg. When we examined BPA derivatives to evaluate the structural essentials required for the binding of BPA to ERR-γ , we found that only one of the two phenol-hydroxyl groups was essential for the full binding. The maximal activity was attained when one of the methyl groups was removed. All of the potent BPA derivatives retained a high constitutive basal activity of ERR-γ in the luciferase reporter gene assay and exhibited a distinct inhibitory activity against 4-OHT.ConclusionThese results indicate that the phenol derivatives are potent candidates for the endocrine disruptor that binds to ERR-γ.

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The regulatory mechanism of bipedal standing in humans remains to be elucidated. We investigated neural substrates for maintaining standing postures in humans using PET with our mobile gantry PET system. Normal volunteers were instructed to adopt several postures: supine with eyes open toward a target; standing with feet together and eyes open or eyes closed; and standing on one foot or with two feet in a tandem relationship with eyes open toward the target. Compared with the supine posture, standing with feet together activated the cerebellar anterior lobe and the right visual cortex (Brodmann area 18/19), and standing on one foot increased cerebral blood flow in the cerebellar anterior vermis and the posterior lobe lateral cortex ipsilateral to the weight-bearing side. Standing in tandem was accompanied by activation within the visual association cortex, the anterior and posterior vermis as well as within the midbrain. Standing with eyes closed activated the prefrontal cortex (Brodmann area 8/9). Our findings confirmed that the cerebellar vermis efferent system plays an important role in maintenance of standing posture and suggested that the visual association cortex may subserve regulating postural equilibrium while standing.

Protracted abuse of methamphetamine may reduce the density of the serotonin transporter in the brain, leading to elevated aggression, even in currently abstinent abusers.