Deletion of SHATI/NAT8L increases dopamine D1 receptor on the cell surface in the nucleus accumbens, accelerating methamphetamine dependence

Kazuya Toriumi, Mizuki Kondo, Taku Nagai, Ryota Hashimoto, Kazutaka Ohi, Ziyu Song, Junko Tanaka, Akihiro Mouri, Takenao Koseki, Hidenaga Yamamori, Yoko Furukawa-Hibi, Takayoshi Mamiya, Takeshi Fukushima, Masatoshi Takeda, Atsumi Nitta, Kiyofumi Yamada, Toshitaka Nabeshima

Research output: Contribution to journalArticle

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Abstract

In a previous report, we identified a novel molecule, SHATI/NAT8L, having an inhibitory effect on methamphetamine (METH)-induced hyperlocomotion, sensitization, and conditioned place preference (CPP). SHATI/NAT8L attenuates the METH-induced increase in dopamine overflow in the nucleus accumbens (NAc) by promoting plasmalemmal and vesicular dopamine uptake. However, the biological functions of the protein remain unclear. In this study, we explored NAT8L-binding proteins using pull-down assays and identified a number of components of the adaptor protein (AP)-2 complex, which is a multimeric protein localized to the plasma membrane that functions to internalize cargo during clathrin-mediated endocytosis. To investigate whether NAT8L regulates the receptor localization to the cell surface, cell-surface dopamine D1 receptor in the NAc of Nat8l knockout (KO) mice was quantified. We found that dopamine D1 receptor on the cell surface was increased in the NAc of Nat8l KO mice compared with the wild type (WT) animals. Consistent with this finding, Nat8l KO mice showed higher basal locomotor activity and heightened sensitivity to D1 agonist compared with WT mice. In addition, METH-induced sensitization and CPP were enhanced in Nat8l KO mice. These results suggest that NAT8L might regulate the localization of cell-surface dopamine D1 receptor, thereby controlling basal behaviour and sensitivity to METH. Furthermore, we observed a single nucleotide polymorphism (SNP) in the human NAT8L gene related to reward dependence, a personality trait, and grey matter volume in the caudate nucleus in healthy subjects, suggesting that NAT8L might also affect human personality.

Original languageEnglish
Pages (from-to)443-453
Number of pages11
JournalInternational Journal of Neuropsychopharmacology
Volume17
Issue number3
DOIs
Publication statusPublished - 01-01-2014
Externally publishedYes

Fingerprint

Dopamine D1 Receptors
Methamphetamine
Nucleus Accumbens
Knockout Mice
Adaptor Protein Complex 2
Personality
Dopamine
Clathrin
Wild Animals
Caudate Nucleus
Locomotion
Endocytosis
Reward
Single Nucleotide Polymorphism
Healthy Volunteers
Carrier Proteins
Proteins
Cell Membrane
Genes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Toriumi, Kazuya ; Kondo, Mizuki ; Nagai, Taku ; Hashimoto, Ryota ; Ohi, Kazutaka ; Song, Ziyu ; Tanaka, Junko ; Mouri, Akihiro ; Koseki, Takenao ; Yamamori, Hidenaga ; Furukawa-Hibi, Yoko ; Mamiya, Takayoshi ; Fukushima, Takeshi ; Takeda, Masatoshi ; Nitta, Atsumi ; Yamada, Kiyofumi ; Nabeshima, Toshitaka. / Deletion of SHATI/NAT8L increases dopamine D1 receptor on the cell surface in the nucleus accumbens, accelerating methamphetamine dependence. In: International Journal of Neuropsychopharmacology. 2014 ; Vol. 17, No. 3. pp. 443-453.
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abstract = "In a previous report, we identified a novel molecule, SHATI/NAT8L, having an inhibitory effect on methamphetamine (METH)-induced hyperlocomotion, sensitization, and conditioned place preference (CPP). SHATI/NAT8L attenuates the METH-induced increase in dopamine overflow in the nucleus accumbens (NAc) by promoting plasmalemmal and vesicular dopamine uptake. However, the biological functions of the protein remain unclear. In this study, we explored NAT8L-binding proteins using pull-down assays and identified a number of components of the adaptor protein (AP)-2 complex, which is a multimeric protein localized to the plasma membrane that functions to internalize cargo during clathrin-mediated endocytosis. To investigate whether NAT8L regulates the receptor localization to the cell surface, cell-surface dopamine D1 receptor in the NAc of Nat8l knockout (KO) mice was quantified. We found that dopamine D1 receptor on the cell surface was increased in the NAc of Nat8l KO mice compared with the wild type (WT) animals. Consistent with this finding, Nat8l KO mice showed higher basal locomotor activity and heightened sensitivity to D1 agonist compared with WT mice. In addition, METH-induced sensitization and CPP were enhanced in Nat8l KO mice. These results suggest that NAT8L might regulate the localization of cell-surface dopamine D1 receptor, thereby controlling basal behaviour and sensitivity to METH. Furthermore, we observed a single nucleotide polymorphism (SNP) in the human NAT8L gene related to reward dependence, a personality trait, and grey matter volume in the caudate nucleus in healthy subjects, suggesting that NAT8L might also affect human personality.",
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Toriumi, K, Kondo, M, Nagai, T, Hashimoto, R, Ohi, K, Song, Z, Tanaka, J, Mouri, A, Koseki, T, Yamamori, H, Furukawa-Hibi, Y, Mamiya, T, Fukushima, T, Takeda, M, Nitta, A, Yamada, K & Nabeshima, T 2014, 'Deletion of SHATI/NAT8L increases dopamine D1 receptor on the cell surface in the nucleus accumbens, accelerating methamphetamine dependence', International Journal of Neuropsychopharmacology, vol. 17, no. 3, pp. 443-453. https://doi.org/10.1017/S1461145713001302

Deletion of SHATI/NAT8L increases dopamine D1 receptor on the cell surface in the nucleus accumbens, accelerating methamphetamine dependence. / Toriumi, Kazuya; Kondo, Mizuki; Nagai, Taku; Hashimoto, Ryota; Ohi, Kazutaka; Song, Ziyu; Tanaka, Junko; Mouri, Akihiro; Koseki, Takenao; Yamamori, Hidenaga; Furukawa-Hibi, Yoko; Mamiya, Takayoshi; Fukushima, Takeshi; Takeda, Masatoshi; Nitta, Atsumi; Yamada, Kiyofumi; Nabeshima, Toshitaka.

In: International Journal of Neuropsychopharmacology, Vol. 17, No. 3, 01.01.2014, p. 443-453.

Research output: Contribution to journalArticle

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T1 - Deletion of SHATI/NAT8L increases dopamine D1 receptor on the cell surface in the nucleus accumbens, accelerating methamphetamine dependence

AU - Toriumi, Kazuya

AU - Kondo, Mizuki

AU - Nagai, Taku

AU - Hashimoto, Ryota

AU - Ohi, Kazutaka

AU - Song, Ziyu

AU - Tanaka, Junko

AU - Mouri, Akihiro

AU - Koseki, Takenao

AU - Yamamori, Hidenaga

AU - Furukawa-Hibi, Yoko

AU - Mamiya, Takayoshi

AU - Fukushima, Takeshi

AU - Takeda, Masatoshi

AU - Nitta, Atsumi

AU - Yamada, Kiyofumi

AU - Nabeshima, Toshitaka

PY - 2014/1/1

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N2 - In a previous report, we identified a novel molecule, SHATI/NAT8L, having an inhibitory effect on methamphetamine (METH)-induced hyperlocomotion, sensitization, and conditioned place preference (CPP). SHATI/NAT8L attenuates the METH-induced increase in dopamine overflow in the nucleus accumbens (NAc) by promoting plasmalemmal and vesicular dopamine uptake. However, the biological functions of the protein remain unclear. In this study, we explored NAT8L-binding proteins using pull-down assays and identified a number of components of the adaptor protein (AP)-2 complex, which is a multimeric protein localized to the plasma membrane that functions to internalize cargo during clathrin-mediated endocytosis. To investigate whether NAT8L regulates the receptor localization to the cell surface, cell-surface dopamine D1 receptor in the NAc of Nat8l knockout (KO) mice was quantified. We found that dopamine D1 receptor on the cell surface was increased in the NAc of Nat8l KO mice compared with the wild type (WT) animals. Consistent with this finding, Nat8l KO mice showed higher basal locomotor activity and heightened sensitivity to D1 agonist compared with WT mice. In addition, METH-induced sensitization and CPP were enhanced in Nat8l KO mice. These results suggest that NAT8L might regulate the localization of cell-surface dopamine D1 receptor, thereby controlling basal behaviour and sensitivity to METH. Furthermore, we observed a single nucleotide polymorphism (SNP) in the human NAT8L gene related to reward dependence, a personality trait, and grey matter volume in the caudate nucleus in healthy subjects, suggesting that NAT8L might also affect human personality.

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