Single cocaine exposure attenuates the intrinsic excitability of CRH neurons in the ventral BNST via Sigma-1 receptors

Jintao Wu; Yue Zhao

doi:10.1515/tnsci-2022-0339

Single cocaine exposure attenuates the intrinsic excitability of CRH neurons in the ventral BNST via Sigma-1 receptors

Transl Neurosci. 2024 Apr 24;15(1):20220339. doi: 10.1515/tnsci-2022-0339. eCollection 2024 Jan 1.

Authors

Jintao Wu^{1

2}, Yue Zhao^{1

3}

Affiliations

¹ School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China.
² School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, China.
³ Liangzhu Laboratory, Zhejiang University Medical Center, MOE Frontier Science Center for Brain Science and Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, Hangzhou, China.

Abstract

The ventral bed nucleus of the stria terminalis (vBNST) plays a key role in cocaine addiction, especially relapse. However, the direct effects of cocaine on corticotropin-releasing hormone (CRH) neurons in the vBNST remain unclear. Here, we identify that cocaine exposure can remarkably attenuate the intrinsic excitability of CRH neurons in the vBNST in vitro. Accumulating studies reveal the crucial role of Sigma-1 receptors (Sig-1Rs) in modulating cocaine addiction. However, to the authors' best knowledge no investigations have explored the role of Sig-1Rs in the vBNST, let alone CRH neurons. Given that cocaine acts as a type of Sig-1Rs agonist, and the dramatic role of Sig-1Rs played in intrinsic excitability of neurons as well as cocaine addiction, we employ BD1063 a canonical Sig-1Rs antagonist to block the effects of cocaine, and significantly recover the excitability of CRH neurons. Together, we suggest that cocaine exposure leads to the firing rate depression of CRH neurons in the vBNST via binding to Sig-1Rs.

Keywords: CRH neurons; Sigma-1 receptors; cocaine; intrinsic excitability; ventral BNST.