Cocaine Augments Dopamine-Mediated Inhibition of Neuronal Activity in the Dorsal Bed Nucleus of the Stria Terminalis

• DOI: 10.1523/jneurosci.0284-21.2021
• Publication Date: 2021-05-25T17:50:16Z
• Authors: James R. Melchior; Rafael E. Perez; Gregory J. Salimando; Joseph R. Luchsinger; Aakash Basu; Danny G. Winder
• Keywords: Autoreceptor; Eticlopride

The dorsal region of the bed nucleus stria terminalis (dBNST) receives substantial dopaminergic input which overlaps with norepinephrine implicated in stress responses. Using <i>ex vivo</i> fast scan cyclic voltammetry male C57BL6 mouse brain slices, we demonstrate that electrically stimulated dBNST catecholamine signals are substantially lower magnitude and have slower uptake rates compared caudate signals. Dopamine terminal autoreceptor activation inhibited roughly half transient, noradrenergic produced an ∼30% inhibition. transporter blockade either cocaine or GBR12909 significantly augmented signal duration. We optogenetically targeted dopamine terminals transgenic (<i>TH:Cre</i>) mice sex and, using whole-cell electrophysiology, optically release induces slow outward membrane currents associated hyperpolarization response a subset neurons. These cellular responses had similar temporal profile to release, were reduced by D2/D3 receptor antagonist raclopride, potentiated cocaine. <i>in fiber photometry C57BL/6 during training sessions for conditioned place preference, show acute administration results significant inhibition calcium transient activity neurons saline administration. data provide evidence mechanism dopamine-mediated augments this while also decreasing net drug reinforcement paradigm. <b>SIGNIFICANCE STATEMENT</b> is highly mediating responses; however, inputs from classically defined reward pathways. Here used various techniques signaling within has inhibitory effects on population activity. cocaine, abused psychostimulant, both region. reduces dBNST, vivo</i>. Together, these support providing means drug-induced elevations may inhibit promote reward.