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- Title
Vagus Nerve Stimulation (VNS) Modulates Synaptic Plasticity in the Infralimbic Cortex via Trk-B Receptor Activation to Reduce Drug-Seeking in Male Rats.
- Authors
Driskill, Christopher M.; Childs, Jessica E.; Phensy, Aarron J.; Rodriguez, Sierra R.; O'Brien, John T.; Lindquist, Kathy L.; Naderi, Aurian; Bordieanu, Bogdan; McGinty, Jacqueline F.; Kroener, Sven
- Abstract
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.
- Subjects
VAGUS nerve stimulation; NEUROPLASTICITY; SUBSTANCE abuse relapse; PYRAMIDAL neurons; BRAIN-derived neurotrophic factor; RATS; DOPAMINE receptors; BIOLOGICAL extinction
- Publication
Journal of Neuroscience, 2024, Vol 44, Issue 23, p1
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0107-24.2024