title: Serotonergic and noradrenergic pathways are required for the anxiolytic-like and antidepressant-like behavioral effects of repeated vagal nerve stimulation in rats.
abstract: 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.
authors: Department of Pharmacology, University of Texas Health Science Center, San Antonio, USA.
authors: Havan
authors: H
authors: Furmaga
authors: Aparna
authors: A
authors: Shah
authors: Alan
authors: A
authors: Frazer
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D018663:Adrenergic Agents / Q000494:pharmacology; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects; D007099:Imipramine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D046353:Immobility Response, Tonic / Q000187:drug effects; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000031:analogs & derivatives* / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000493:pharmacokinetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D020280:Sertraline / Q000494:pharmacology; D013550:Swimming / Q000523:psychology; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics; D055536:Vagus Nerve Stimulation
chemical_list: D015116:5,7-Dihydroxytryptamine; D018663:Adrenergic Agents; D018759:Adrenergic Uptake Inhibitors; D003891:Desipramine; D007099:Imipramine; D009638:Norepinephrine; D016627:Oxidopamine; D012701:Serotonin; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D014316:Tritium; C024316:cianopramine; C002748:noradrenalone