Glutamatergic neurons in the medial prefrontal cortex mediate the formation and retrieval of cocaine-associated memories in mice

Tong Zhang, Junko Yanagida, Hironori Kamii, Shintaro Wada, Masaki Domoto, Hitoki Sasase, Satoshi Deyama, Takeshi Takarada, Eiichi Hinoi, Kenji Sakimura, Akihiro Yamanaka, Takashi Maejima, Michihiro Mieda, Takeshi Sakurai, Naoya Nishitani, Kazuki Nagayasu, Shuji Kaneko, Masabumi Minami, Katsuyuki Kaneda

Research output: Contribution to journalArticle

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Abstract

In drug addiction, environmental stimuli previously associated with cocaine use readily elicit cocaine-associated memories, which persist long after abstinence and trigger cocaine craving and consumption. Although previous studies suggest that the medial prefrontal cortex (mPFC) is involved in the expression of cocaine-addictive behaviors, it remains unclear whether excitatory and inhibitory neurons in the mPFC are causally related to the formation and retrieval of cocaine-associated memories. To address this issue, we used the designer receptors exclusively activated by designer drugs (DREADD) technology combined with a cocaine-induced conditioned place preference (CPP) paradigm. We suppressed mPFC neuronal activity in a cell-type– and timing-dependent manner. C57BL/6J wild-type mice received bilateral intra-mPFC infusion of an adeno-associated virus (AAV) expressing inhibitory DREADD (hM4Di) under the control of CaMKII promotor to selectively suppress mPFC pyramidal neurons. GAD67-Cre mice received bilateral intra-mPFC infusion of a Cre-dependent AAV expressing hM4Di to specifically silence GABAergic neurons. Chemogenetic suppression of mPFC pyramidal neurons significantly attenuated both the acquisition and expression of cocaine CPP, while suppression of mPFC GABAergic neurons affected neither the acquisition nor expression of cocaine CPP. Moreover, chemogenetic inhibition of mPFC glutamatergic neurons did not affect the acquisition and expression of lithium chloride-induced conditioned place aversion. These results suggest that the activation of glutamatergic, but not GABAergic, neurons in the mPFC mediates both the formation and retrieval of cocaine-associated memories.

Original languageEnglish
JournalAddiction Biology
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Prefrontal Cortex
Cocaine
Neurons
GABAergic Neurons
Designer Drugs
Dependovirus
Pyramidal Cells
Addictive Behavior
Lithium Chloride
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Substance-Related Disorders
Technology

Keywords

  • addiction
  • cocaine
  • DREADD
  • glutamate
  • medial prefrontal cortex
  • memory

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health

Cite this

Glutamatergic neurons in the medial prefrontal cortex mediate the formation and retrieval of cocaine-associated memories in mice. / Zhang, Tong; Yanagida, Junko; Kamii, Hironori; Wada, Shintaro; Domoto, Masaki; Sasase, Hitoki; Deyama, Satoshi; Takarada, Takeshi; Hinoi, Eiichi; Sakimura, Kenji; Yamanaka, Akihiro; Maejima, Takashi; Mieda, Michihiro; Sakurai, Takeshi; Nishitani, Naoya; Nagayasu, Kazuki; Kaneko, Shuji; Minami, Masabumi; Kaneda, Katsuyuki.

In: Addiction Biology, 01.01.2019.

Research output: Contribution to journalArticle

Zhang, T, Yanagida, J, Kamii, H, Wada, S, Domoto, M, Sasase, H, Deyama, S, Takarada, T, Hinoi, E, Sakimura, K, Yamanaka, A, Maejima, T, Mieda, M, Sakurai, T, Nishitani, N, Nagayasu, K, Kaneko, S, Minami, M & Kaneda, K 2019, 'Glutamatergic neurons in the medial prefrontal cortex mediate the formation and retrieval of cocaine-associated memories in mice', Addiction Biology. https://doi.org/10.1111/adb.12723
Zhang, Tong ; Yanagida, Junko ; Kamii, Hironori ; Wada, Shintaro ; Domoto, Masaki ; Sasase, Hitoki ; Deyama, Satoshi ; Takarada, Takeshi ; Hinoi, Eiichi ; Sakimura, Kenji ; Yamanaka, Akihiro ; Maejima, Takashi ; Mieda, Michihiro ; Sakurai, Takeshi ; Nishitani, Naoya ; Nagayasu, Kazuki ; Kaneko, Shuji ; Minami, Masabumi ; Kaneda, Katsuyuki. / Glutamatergic neurons in the medial prefrontal cortex mediate the formation and retrieval of cocaine-associated memories in mice. In: Addiction Biology. 2019.
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abstract = "In drug addiction, environmental stimuli previously associated with cocaine use readily elicit cocaine-associated memories, which persist long after abstinence and trigger cocaine craving and consumption. Although previous studies suggest that the medial prefrontal cortex (mPFC) is involved in the expression of cocaine-addictive behaviors, it remains unclear whether excitatory and inhibitory neurons in the mPFC are causally related to the formation and retrieval of cocaine-associated memories. To address this issue, we used the designer receptors exclusively activated by designer drugs (DREADD) technology combined with a cocaine-induced conditioned place preference (CPP) paradigm. We suppressed mPFC neuronal activity in a cell-type– and timing-dependent manner. C57BL/6J wild-type mice received bilateral intra-mPFC infusion of an adeno-associated virus (AAV) expressing inhibitory DREADD (hM4Di) under the control of CaMKII promotor to selectively suppress mPFC pyramidal neurons. GAD67-Cre mice received bilateral intra-mPFC infusion of a Cre-dependent AAV expressing hM4Di to specifically silence GABAergic neurons. Chemogenetic suppression of mPFC pyramidal neurons significantly attenuated both the acquisition and expression of cocaine CPP, while suppression of mPFC GABAergic neurons affected neither the acquisition nor expression of cocaine CPP. Moreover, chemogenetic inhibition of mPFC glutamatergic neurons did not affect the acquisition and expression of lithium chloride-induced conditioned place aversion. These results suggest that the activation of glutamatergic, but not GABAergic, neurons in the mPFC mediates both the formation and retrieval of cocaine-associated memories.",
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AU - Zhang, Tong

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AU - Wada, Shintaro

AU - Domoto, Masaki

AU - Sasase, Hitoki

AU - Deyama, Satoshi

AU - Takarada, Takeshi

AU - Hinoi, Eiichi

AU - Sakimura, Kenji

AU - Yamanaka, Akihiro

AU - Maejima, Takashi

AU - Mieda, Michihiro

AU - Sakurai, Takeshi

AU - Nishitani, Naoya

AU - Nagayasu, Kazuki

AU - Kaneko, Shuji

AU - Minami, Masabumi

AU - Kaneda, Katsuyuki

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N2 - In drug addiction, environmental stimuli previously associated with cocaine use readily elicit cocaine-associated memories, which persist long after abstinence and trigger cocaine craving and consumption. Although previous studies suggest that the medial prefrontal cortex (mPFC) is involved in the expression of cocaine-addictive behaviors, it remains unclear whether excitatory and inhibitory neurons in the mPFC are causally related to the formation and retrieval of cocaine-associated memories. To address this issue, we used the designer receptors exclusively activated by designer drugs (DREADD) technology combined with a cocaine-induced conditioned place preference (CPP) paradigm. We suppressed mPFC neuronal activity in a cell-type– and timing-dependent manner. C57BL/6J wild-type mice received bilateral intra-mPFC infusion of an adeno-associated virus (AAV) expressing inhibitory DREADD (hM4Di) under the control of CaMKII promotor to selectively suppress mPFC pyramidal neurons. GAD67-Cre mice received bilateral intra-mPFC infusion of a Cre-dependent AAV expressing hM4Di to specifically silence GABAergic neurons. Chemogenetic suppression of mPFC pyramidal neurons significantly attenuated both the acquisition and expression of cocaine CPP, while suppression of mPFC GABAergic neurons affected neither the acquisition nor expression of cocaine CPP. Moreover, chemogenetic inhibition of mPFC glutamatergic neurons did not affect the acquisition and expression of lithium chloride-induced conditioned place aversion. These results suggest that the activation of glutamatergic, but not GABAergic, neurons in the mPFC mediates both the formation and retrieval of cocaine-associated memories.

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