title: Vagus nerve stimulation reduces cocaine seeking and alters plasticity in the extinction network.
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 rates of relapse. Here we used vagus nerve stimulation (VNS) to induce targeted synaptic plasticity to facilitate extinction of appetitive behaviors and to reduce relapse. Rats self-administered cocaine and were given VNS during extinction. Relapse to drug-seeking was assessed in a cued reinstatement session. We used immunohistochemistry to measure changes in the expression of the phosphorylated transcription factor cAMP response-element binding protein (pCREB) in the PFC and the basolateral amygdala (BLA), which regulate cue learning and extinction. In vivo recordings of evoked field potentials measured drug- and VNS-induced changes in metaplasticity in the pathway from the PFC to the BLA. VNS-treated rats showed improved rates of extinction and reduced reinstatement. Following reinstatement, pCREB levels were reduced in the IL and BLA of VNS-treated rats. Evoked responses in the BLA were greatly reduced in VNS-treated rats, and these rats were also resistant to the induction of LTD. Taken together, these results show that VNS facilitates extinction and reduces reinstatement. Changes in the pathway between the PFC and the amygdala may contribute to these beneficial effects.
authors.affiliation: School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, Texas 75080, USA.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Childs
authors.affiliation: School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, Texas 75080, USA.
authors.forename: Jaime
authors.initials: J
authors.lastname: DeLeon
authors.affiliation: School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, Texas 75080, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Nickel
authors.affiliation: School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, Texas 75080, USA kroener@utdallas.edu.
authors.forename: Sven
authors.identifier: 0000-0003-1728-8111
authors.initials: S
authors.lastname: Kroener
mesh_terms: D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D058999:Drug-Seeking Behavior / Q000187:drug effects* / Q000502:physiology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005502:Food; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D055536:Vagus Nerve Stimulation
chemical_list: D000779:Anesthetics, Local; D050882:CREB-Binding Protein; D003042:Cocaine