4.8 Article

Striatal dopamine D1-type receptor availability: no difference from control but association with cortical thickness in methamphetamine users

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MOLECULAR PSYCHIATRY
卷 23, 期 5, 页码 1320-1327

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SPRINGERNATURE
DOI: 10.1038/mp.2017.172

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资金

  1. National Institute on Drug Abuse [K23 DA027734, R21 DA034928]
  2. Thomas P and Katherine K Pike Chair in Addiction Studies
  3. Marjorie M Greene Trust
  4. Department of Psychiatry, Graduate School of Medicine, Chiba University, DOMONKAI fund

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Chronic methamphetamine use poses potentially devastating consequences for directly affected individuals and for society. Lower dopamine D2-type receptor availability has been observed in striata of methamphetamine users as compared with controls, but an analogous comparison of D1-type receptors has been conducted only on post-mortem material, with no differences in methamphetamine users from controls in the caudate nucleus and putamen and higher D1-receptor density in the nucleus accumbens. Released from neurons when methamphetamine is self-administered, dopamine binds to both D1- and D2-type receptors in the striatum, with downstream effects on cortical activity. Thus, both receptor subtypes may contribute to methamphetamine-induced alterations in cortical morphology and behavior. In this study, 21 methamphetamine-dependent subjects and 23 healthy controls participated in positron emission tomography and structural magnetic resonance imaging for assessment of striatal D1-and D2-type receptor availability and cortical gray-matter thickness, respectively. Although D2-type receptor availability (BPnd) was lower in the methamphetamine group, as shown previously, the groups did not differ in D1-type BPnd. In the methamphetamine group, mean cortical gray-matter thickness was negatively associated with cumulative methamphetamine use and craving for the drug. Striatal D1-type but not D2-type BPnd was negatively associated with global mean cortical gray-matter thickness in the methamphetamine group, but no association was found between gray-matter thickness and BPnd for either dopamine receptor subtype in the control group. These results suggest a role of striatal D1-type receptors in cortical adaptation to chronic methamphetamine use.

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