Acute 5 Hz deep brain stimulation of the lateral habenula is associated with depressive-like behavior in male wild-type Wistar rats

Abstract

Background: Chronic high frequency Deep Brain Stimulation (DBS) of the Lateral Habenula (LHb) has been applied in clinical case studies to treat patients with treatment resistant depression. LHb neurons in models of depression were found to have a preferred firing frequency in the theta band. The aim of this study was to determine differential behavioral effects of acute high- and theta band-frequency DBS and whether bilateral DBS electrode insertion may be associated with a lesional effect.

Methods: Adult male Wistar rats were implanted with bilateral LHb DBS electrodes and randomly assigned to 100 Hz, 5 Hz or sham stimulation (n = 8 per group). Rats were tested against a control group (n = 8) in a battery of behavioral paradigms.

Results: No differences between groups were found with regards to locomotor activity in the open field test or anhedonia-like behavior in the novelty suppressed feeding paradigm. 100 Hz stimulation was associated with increased exploratory behavior in the elevated plus maze. In the forced swim test, 5 Hz stimulation was associated with significantly decreased latency to and increased duration of immobility, whereas 100 Hz stimulation significantly increased latency to immobility. No significant behavioral differences between sham stimulation and control group animals were detected.

Conclusion: Acute theta band frequency DBS in the LHb is associated with depressive-like behavior in wild-type male Wistar rats. This was likely not mediated by a general decrease in locomotor activity or a lesional effect after electrode implantation.

Keywords: Behavior; Deep brain stimulation; Depression; Lateral habenula; Rat.