Vagus Nerve Stimulation (VNS) Modulates Synaptic Plasticity in the Infralimbic Cortex via Trk-B Receptor Activation to Reduce Drug-Seeking in Male Rats.

Autor:	Driskill CM; School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, Texas 75080., Childs JE; School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, Texas 75080., Phensy AJ; School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, Texas 75080., Rodriguez SR; School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, Texas 75080., O'Brien JT; School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, Texas 75080., Lindquist KL; School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, Texas 75080., Naderi A; School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, Texas 75080., Bordieanu B; Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425., McGinty JF; Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425., Kroener S; School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, Texas 75080 kroener@utdallas.edu.
Jazyk:	angličtina
Zdroj:	The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2024 Jun 05; Vol. 44 (23). Date of Electronic Publication: 2024 Jun 05.
DOI:	10.1523/JNEUROSCI.0107-24.2024
Abstrakt:	Drugs of abuse cause changes in the prefrontal cortex (PFC) and associated regions that impair inhibitory control over drug-seeking. Breaking the contingencies between drug-associated cues and the delivery of the reward during extinction learning reduces relapse. Vagus nerve stimulation (VNS) has previously been shown to enhance extinction learning and reduce drug-seeking. Here we determined the effects of VNS-mediated release of brain-derived neurotrophic factor (BDNF) on extinction and cue-induced reinstatement in male rats trained to self-administer cocaine. Pairing 10 d of extinction training with VNS facilitated extinction and reduced drug-seeking behavior during reinstatement. Rats that received a single extinction session with VNS showed elevated BDNF levels in the medial PFC as determined via an enzyme-linked immunosorbent assay. Systemic blockade of tropomyosin receptor kinase B (TrkB) receptors during extinction, via the TrkB antagonist ANA-12, decreased the effects of VNS on extinction and reinstatement. Whole-cell recordings in brain slices showed that cocaine self-administration induced alterations in the ratio of AMPA and NMDA receptor-mediated currents in Layer 5 pyramidal neurons of the infralimbic cortex (IL). Pairing extinction with VNS reversed cocaine-induced changes in glutamatergic transmission by enhancing AMPAR currents, and this effect was blocked by ANA-12. Our study suggests that VNS consolidates the extinction of drug-seeking behavior by reversing drug-induced changes in synaptic AMPA receptors in the IL, and this effect is abolished by blocking TrkB receptors during extinction, highlighting a potential mechanism for the therapeutic effects of VNS in addiction. Competing Interests: The authors declare no competing financial interests. (Copyright © 2024 the authors.)
Databáze:	MEDLINE
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