Background
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.
Methods
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).
Results
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.
Conclusions
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.
Key Words
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Article info
Publication history
Published online: September 12, 2011
Accepted:
July 18,
2011
Received in revised form:
June 29,
2011
Received:
May 2,
2011
Identification
Copyright
© 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
