A study of the effects of vagus nerve stimulation on anxiety in laboratory rats.

摘要

When anxiety becomes excessive and sustained it constitutes a disorder that is debilitating and difficult to treat. Previous research conducted in our laboratory suggested that in addition to enhancing memory processes, electrical stimulation of the vagus nerve in rats also attenuates anxiety-related behaviors. The purpose of the present study was to explore further the capacity of vagus nerve stimulation (VNS) to attenuate behaviors associated with anxiety. Another goal was to determine whether VNS (1.0 mA; 0.5 ms biphasic pulse width; 20 Hz; 30 sec train) produces its effects by activating descending parasympathetic efferent fibers. If a subcutaneous injection (0.1 mg/kg; 0.5 mg/kg; 1.0 mg/kg) of atropine methyl nitrate (AMN, a cholinergic muscarinic receptor antagonist that does not cross the blood-brain barrier) attenuated the effects of VNS, this finding would suggest that VNS acts by causing an increase in parasympathetic tone, specifically an increase in vagal tone. One week before behavioral testing, 96 male Long-Evans rats were implanted with a bipolar stimulating electrode. After the recovery period, animals received two days of baseline testing on each of three measures of anxiety: open field, elevated plus-maze, and predator scent exposure task. Five minutes before each baseline session, the animal was placed in a shock box and a mild footshock (0.75 mA; 1.0 sec) was delivered to induce anxiety. On Day Three, 30 minutes prior to testing, each animal was administered either saline or AMN while unrestrained in its home cage. Twenty minutes later, VNS or sham stimulation was delivered via the head post while the animal moved freely in its home cage. Drug and stimulation effects were examined using a between-subjects MANOVA to analyze the mean scores of Day 3 data. The results indicated that VNS had a robust and significant effect on all nine central behaviors measured. Atropine methyl nitrate at the high dose, and in some cases at the medium dose, had some capacity to attenuate the effects of VNS on most central behaviors. Rats administered AMN and no stimulation showed more anxiety than saline-treated sham-stimulated animals. These results provide some support for the hypotheses tested in the present study.