Archival Report| Volume 70, ISSUE 10, P937-945, November 15, 2011

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Serotonergic and Noradrenergic Pathways Are Required for the Anxiolytic-like and Antidepressant-like Behavioral Effects of Repeated Vagal Nerve Stimulation in Rats

  • Havan Furmaga
    Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas
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  • Aparna Shah
    Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas
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  • Alan Frazer
    Address correspondence to Alan Frazer, Ph.D., Department of Pharmacology, University of Texas Health Science Center, 7703 Floyd Curl Drive, Mail Code 7764, San Antonio, TX 78229-3900
    Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas

    Audie L. Murphy Division, South Texas Veterans Health Care System, San Antonio, Texas
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Published:September 12, 2011DOI:


      Vagal nerve stimulation (VNS) is used for treatment-refractory depression, but there are few preclinical studies of its effects when administered repeatedly over time using clinically relevant stimulation parameters in nonanesthetized animals.


      The novelty-suppressed feeding test (NSFT) and forced swim test (FST) were used to evaluate the anxiolytic- and antidepressant-like potential of VNS in rats, respectively. The behavioral effects of VNS were compared with those of desipramine (DMI; 10 mg/kg/day) and sertraline (7.5 mg/kg/day) administered via osmotic minipump. Such experiments were carried out in intact rats as well as those that had selective destruction of either serotonin or noradrenergic neurons in brain caused by the neurotoxins, 5,7-dihyroxytryptamine (5,7-DHT), or 6-hydroxydopamine (6-OHDA).


      Repeated administration of VNS, DMI, and sertraline decreased latency to feed in the NSFT. In the FST, repeated VNS, DMI, and sertraline caused decreased immobility; the VNS-induced decrease in immobility resulted from increases in both swimming and climbing behaviors. Effects of VNS and sertraline, but not DMI, in both the NSFT and the FST were abolished in rats treated with 5,7-DHT. Effects of DMI in both behavioral tests, but not those of sertraline, were abolished in 6-OHDA treated rats. VNS effects on immobility and climbing in the FST were not blocked in the 6-OHDA-treated rats. There was no significant difference in locomotor activity caused by any of the treatments or by the lesions.


      Serotonergic nerves are required for repeated VNS-induced anxiolytic- and antidepressant-like effects. Noradrenergic nerves can also be activated by VNS to cause its anxiolytic-like effect.

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