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

TL;DR

Cocaine reduces the activity of CRH neurons in the vBNST by acting on Sigma-1 receptors, which could help explain addiction relapse.

Contribution

This study is the first to show that Sigma-1 receptors mediate cocaine's effect on CRH neuron excitability in the vBNST.

Findings

Cocaine exposure reduces the intrinsic excitability of CRH neurons in the vBNST.

Blocking Sigma-1 receptors with BD1063 reverses cocaine's effect on CRH neuron firing rates.

Sigma-1 receptors are critical for cocaine's impact on vBNST CRH neurons.

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.

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