Low frequency deep brain stimulation in the inferior colliculus ameliorates haloperidol-induced catalepsy and reduces anxiety in rats

PLoS One. 2020 Dec 4;15(12):e0243438. doi: 10.1371/journal.pone.0243438. eCollection 2020.

Abstract

Deep brain stimulation (DBS) of the colliculus inferior (IC) improves haloperidol-induced catalepsy and induces paradoxal kinesia in rats. Since the IC is part of the brain aversive system, DBS of this structure has long been related to aversive behavior in rats limiting its clinical use. This study aimed to improve intracollicular DBS parameters in order to avoid anxiogenic side effects while preserving motor improvements in rats. Catalepsy was induced by systemic haloperidol (0.5mg/kg) and after 60 min the bar test was performed during which a given rat received continuous (5 min, with or without pre-stimulation) or intermittent (5 x 1 min) DBS (30Hz, 200-600μA, pulse width 100μs). Only continuous DBS with pre-stimulation reduced catalepsy time. The rats were also submitted to the elevated plus maze (EPM) test and received either continuous stimulation with or without pre-stimulation, or sham treatment. Only rats receiving continuous DBS with pre-stimulation increased the time spent and the number of entries into the open arms of the EPM suggesting an anxiolytic effect. The present intracollicular DBS parameters induced motor improvements without any evidence of aversive behavior, pointing to the IC as an alternative DBS target to induce paradoxical kinesia improving motor deficits in parkinsonian patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / chemically induced
  • Anxiety / physiopathology
  • Anxiety / therapy*
  • Catalepsy / chemically induced
  • Catalepsy / physiopathology
  • Catalepsy / therapy*
  • Deep Brain Stimulation / methods*
  • Disease Models, Animal
  • Haloperidol / toxicity
  • Male
  • Rats
  • Rats, Wistar

Substances

  • Haloperidol

Grants and funding

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This research was supported by a grant from the German Research Foundation to L.M.T. (Deutsche Forschungsgemeinschaft: DFG; ME4197/2-1).